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Spontaneous gasping produces carotid blood flow during untreated cardiac arrest
Resuscitation (2007) 75, 366—371
EXPERIMENTAL PAPER
Spontaneous gasping produces carotid blood flow during untreated cardiac arrest夽 Giuseppe Ristagno a, Wanchun Tang a,b,∗, Shijie Sun a,b, Max Harry Weil a,b,c a
Weil Institute of Critical Care Medicine, Rancho Mirage, CA, United States Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States c Northwestern University, Feinberg School of Medicine, Chicago, IL, United States b
Received 25 January 2007 ; received in revised form 13 April 2007; accepted 19 April 2007 KEYWORDS Cardiac arrest; Gasping; Carotid blood flow; Intrathoracic pressure
Summary Objectives: Coincident with ‘‘agonal’’ gasping during cardiac arrest, there are prominent increases in stroke volumes even in the absence of chest compression. In the present study, we tested the hypothesis that gasps also increase carotid blood flow (CBF) during untreated cardiac arrest. Materials and methods: The tracheas of nine domestic male pigs, weighing 39 ± 2 kg, were intubated and animals were ventilated mechanically. Ventricular fibrillation (VF) was induced electrically and untreated for 5 min. Coincident with the onset of VF, mechanical ventilation was discontinued. The right femoral artery and vein were cannulated. Intrathoracic pressure (ITP) was measured with the aid of a balloon tipped catheter advanced into the esophagus for a distance of 35 cm. A transonic flowprobe was placed around the right common carotid artery for measurement of CBF. Results: Gasps increased in frequency during the first 4 min of untreated VF together with increases in CBF. The CBF produced by gasping averaged 220 ± 102 mL/min, which represented approximately 59% of a pre-cardiac arrest CBF. Significant increases in CBF were highly correlated with the decreases in ITP during the inspiratory phase of the gaspings (r = 0.78) and with the increases in aortic pressure during the expiratory phase of the gaspings (r = 0.76). Conclusions: Spontaneous gasps produce significant increases in CBF during untreated cardiac arrest. The present study therefore confirmed beneficial effects of gasping during cardiac arrest. © 2007 Elsevier Ireland Ltd. All rights reserved.
夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at 10.1016/j.resuscitation.2007.04.020. ∗ Corresponding author at: Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, United States. Tel.: +1 760 778 4911; fax: +1 760 778 3468. E-mail address: [email protected] (W. Tang).
0300-9572/$ — see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.resuscitation.2007.04.020
Spontaneous gasping produces carotid blood flow during untreated cardiac arrest
Introduction Gasping is a striking ‘‘agonal’’ respiratory phenomenon characterized by forceful inspirations, which are often observed in the dramatic conditions of sudden cardiac arrest.1,2 In both experimental and clinical reports the presence and the frequency of gasping were predictive of the success of resuscitation.2,3 Accordingly, gasping is considered an ‘‘autoresuscitative’’ phenomenon triggered by hypoxia,4,5 which persists until respiratory centers located in the caudal portion of the medulla oblongata are disabled.6,7 In experimental models of induced apnea, gasping appeared after an interval of approximately 2 min, when the arterial oxygen tension (PaO2 ) decreased below 5 mmHg. This agonal breathing was able to improve PaO2 to over 30 mmHg promptly and thereby resuming regular respiration.5 Gasping promotes entry of the air into the lungs, securing greater oxygen and CO2 exchange. In a porcine model of cardiac arrest, spontaneous gasping was able to generate more than 4 L/min of ventilation.8 Moreover, gasping has been shown to provide another and probably important source of pulmonary gas exchange during CPR.8—10 More frequent gaspings accounted for greater PaO2 and lower arterial CO2 tensions, when precordial compression, combined with oxygen supplied at the port of the tracheal tube, was the only resuscitative intervention.10 We have documented previously the hemodynamic effects of gasping during untreated cardiac arrest. The expiratory phase of gasping is associated with increases in arterial pressure and in coronary perfusion pressure (CPP).1 Nevertheless, earlier reports have demonstrated that gasping improves not only ventilation but generates cardiac output during untreated cardiac arrest.10,11 Based on the favourable hemodynamic effects which follow each gasp, we therefore previously anticipated that gasping would facilitate increased cerebral perfusion.1 In the present study we investigated the effects of gasping on generation of carotid blood flow (CBF). We hypothesized that gasping would be able to produce increases in CBF during untreated cardiac arrest.
Materials and methods The experiments were performed in an established porcine model of cardiac arrest.12—14 All animals
367
received humane care in compliance with the ‘‘Principles of Laboratory Animal Care’’ formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH publication 86—32, revised 1985). The protocol was approved by the Institutional Animal Care and Use Committee of the Weil Institute of Critical Care Medicine. The animal laboratories of the Institute are fully accredited by American Association for Accreditation of Laboratory Animal Care (AAALAC) International. Nine Yorkshire-cross male domestic pigs (Sus scrofa) weighing 39 ± 2 kg were fasted overnight except for free access to water. Anesthesia was initiated by intramuscular injection of ketamine (20 mg/kg) and completed by ear vein injection of sodium pentobarbital (30 mg/kg). Additional doses of sodium pentobarbital (8 mg/kg) were injected at intervals of approximately 1 h to maintain anesthesia. A cuffed tracheal tube was advanced into the trachea and animals were mechanically ventilated with a volume-controlled ventilator (Model MA-1, Puritan-Bennett, Carlsbad, CA), with a tidal volume of 15 mL/kg, peak flow of 40 L/min, and FiO2 of 0.21. End-tidal PCO2 (EtPCO2 ) was monitored with an infrared capnometer (Model NPB-75, Nellcor Puritan Bennett Inc., Pleasanton, CA). Respiratory frequency was adjusted to maintain EtPCO2 between 35 and 40 mmHg. For measurement of mean aortic pressure (MAP), a fluid filled 8-Fr angiographic catheter (model 6523; USCI C.R. Bard, Inc., Salt Lake City, UT) was advanced from the right femoral artery into the thoracic aorta. For the measurements of right atrial pressure (RAP) a 7-Fr balloon tipped catheter (Abbott Critical Care 41216) with an atrial port was advanced from the right femoral vein and flow directed into pulmonary artery. Conventional external pressure transducers were used (Transpac IV, Abbott Critical Care Systems, North Chicago, IL). For measurement of intrathoracic pressure (ITP) a balloon tipped catheter, connected to a pressure transducer, was advanced from the incisor teeth into the esophagus for a distance of 35 cm.15 CBF was measured continuously with the aid of a flowprobe (Ultrasonic Blood Flow Meter, T101, Transonic Systems Inc., Ithaca, NY) positioned around the right common carotid artery. To induce VF, a 5-Fr pacing catheter (EP Technologies, Inc., Mountain View, CA) was advanced from the surgically exposed right cephalic vein into the right ventricle. The catheter subsequently was advanced into the apex of the right ventricle with the aid of an image intensifier. To measure the scalar
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electrocardiogram, three adhesive electrodes were applied to the shaved skin of the right and left infraclavicular areas and the left lower abdomen. Cardiac arrest was induced with 1 mA alternating current delivered to the endocardium of the right ventricle. After onset of VF, the pacing catheter was removed and mechanical ventilation was discontinued. VF was maintained for 5 min without any intervention, except for the tracheal tube that was maintained in position. Hemodynamic data, CBF, EtPCO2 , ITP and ECG were continuously measured and recorded on a PCbased data acquisition system supported by CODAS hardware/software as previously described.16 CPP was digitally computed from the differences in time-coincident diastolic aortic and right atrial pressures and displayed in real time.
Statistical analyses All data are presented as mean ± S.D. For comparisons between time-based measurements within the groups, analysis of variance was used for repeated measurements. Linear correlations were calculated using the Pearson correlation coefficient. A p value < 0.05 was regarded as statistically significant.
Results All the animals presented with gasping during the 5 min interval of untreated cardiac arrest and gasping followed a crescendo—decrescendo pattern. Over the 5 min interval of untreated VF, gaspings increased CBF together with aortic pressure and EtPCO2 , and decreased right atrial pressures, as shown in Figure 1. The inspiratory phase of gasping was characterized by significant decreases in ITP which were accompanied by corresponding decreases of pressures in the aorta and right atrium. Following the expiratory phase, significant increases in aortic, right atrial and CPP were observed (p < 0.0001), together with increases in EtPCO2 (p < 0.0001), as detailed in Table 1. Gasping significantly increased in frequency over the minutes of untreated cardiac arrest, from 0 during the first min to 7 during the fourth minute (Figure 2). Such increases in the frequency of gasping were accompanied by significantly greater decreases in ITP during the inspiratory phase of gasping (p < 0.01) and significantly greater increases in aortic pressure during the expiratory phase of gasping (p < 0.01), as shown in Figure 3.
Figure 1 Effects of gasping on CBF, aortic and right atrial pressures and EtPCO2 during 5 min interval of untreated VF.
CBF produced by each gasp, significantly increased over the period of untreated VF (Figure 4), from 119 ± 59 mL/min during the second min of VF to 224 ± 111 mL/min in the fifth minute of VF (p < 0.01). Over the 5 min interval of untreated cardiac arrest, CBF generated by gasping averaged 220 ± 102 mL/min. These values represented approximately 59% of the CBF generated from the beating heart, which was 367 ± 64 mL/min (p < 0.01).
Figure 2 Increases in frequency of gaspings over 5 min interval of untreated VF *p < 0.05 and **p < 0.01 vs. VF 2 min; † p < 0.01 vs. VF 1 min.
Spontaneous gasping produces carotid blood flow during untreated cardiac arrest
369
Table 1 Effects of inspiratory and expiratory phases of gasping on aortic, right atrial, coronary perfusion and intrathoracic pressures and end-tidal PCO2 during untreated VF Gasping
Prior to gasping
Aortic pressure (mmHg) Right atrial pressure (mmHg) Coronary perfusion pressure (mmHg) Intrathoracic pressure (mmHg) End-tidal PCO2 (mmHg)
20 16 3 2 1
± ± ± ± ±
Inspiration −1 1 −2 −20 1
3 4 3 3 1
± ± ± ± ±
15* 8* 14 15* 1
Expiration 39 29 10 10 13
± ± ± ± ±
8† 4† 8† 6† 3†
*p < 0.0001 vs. ‘‘prior to gasping’’. † p < 0.0001 vs. ‘‘prior to gasping’’ and ‘‘inspiration’’.
Figure 3 Increases in CBF produced by gasps over 5 min interval of untreated VF. *p < 0.01 vs. VF 2 min; † p < 0.05 vs. VF 3 min.
Figure 5 Linear correlation between CBF generated by gasping with decreases in ITP during the inspiratory phase of gasping and with increases in aortic pressure generated during the expiratory phase of gasping.
Increases in CBF generated by gasping were highly correlated with the decreases in ITP (r = 0.78, p < 0.01) observed during the inspiration phase of the gasping and with the increases in aortic pressure (r = 0.76, p < 0.01) during the expiratory phase of gasping (Figure 5).
Discussion
Figure 4 Effects of gasping on ITP and aortic pressure during 5 min interval of untreated VF. Decreases in ITP and increases in aortic pressure followed each gasping. § p < 0.01 vs. VF 1 min; *p < 0.01 vs. VF 2 min and VF 5 min; † p < 0.05 vs. VF 2 min.
Gasping began after the first min of cardiac arrest and increased in frequency during the first 4 min of untreated VF together with increases in CBF. The CBF generated by gasping averaged approximately 59% of pre-cardiac arrest CBF. These significant increases in CBF were highly correlated with the decreases in ITP observed during the inspiratory phase of the gasping and with the increases in aortic pressure that typically followed the expiratory phase of the gasping.
370 Generation of CBF by gasping is explained by the hemodynamic effects that followed each gasp. During the inspiratory phase, forceful contraction of inspiratory muscles produced decreases in ITP of more than 20 mmHg and thereby favoured the venous return to the heart and ultimately to the preload.17 Such decreases in ITP were, in fact, accompanied by decreases in right atrial pressure of more than 15 mmHg, generating therefore a pressure gradient between the peripheral veins and the right atrium. Following the expiratory phase of the gasping, we observed increases in ITP that were accompanied by increases in aortic pressure of more than 38 mmHg, which were greater than increases in right atrial pressure and thereby accounted for increases in CPP. Moreover, it has recently been reported that spontaneous gasping during cardiac arrest produces significant decreases in intra-cranial pressure, which averaged 7 mmHg, along with significant increases in cerebral perfusion pressure, of approximately 11 mmHg.18 These mechanisms might also account for the generation of CBF during gasping. The present findings confirm previous observations of beneficial effects of gasping. Increases in aortic pressure and CPP have been shown to be highly related with stroke volumes generated by gasping. During its expiratory phase in fact gasping generates stroke volumes that are approximately 60% of the spontaneously beating heart.11 Increases in EtPCO2 coincident with each gasp also reflect increases in pulmonary blood flow and therefore increases in cardiac output.19 In our study such increases in EtCO2 were confirmed and the CBF produced by gasping was approximately 59% of the pre-arrest flow, values which are consistent with previously reported amounts of echocardiographically measured stroke volumes produced by gasping.11 In clinical settings, presence of gasping has also been associated with successful resuscitation and increased survival.2,20,21 Agonal respiration has been reported in human victims of cardiac arrest with an incidence of more than 55% of witnessed sudden deaths.21 In 445 instances of sudden death, agonal respirations had been reported in 40% of the victims; 27% of patients who presented with gasping were successfully discharged from the hospital, compared with only 9% of the patients who did not gasp.2 Gasps have been associated with witnessed events, VF, and survival, suggesting that agonal respiration is a marker of an arrest’s early phase.22 This is consistent with our report in which a crescendo—decrescendo pattern was observed, with gradual increases of the hemodynamic effects
G. Ristagno et al. of the gasping over the initial 4 min of VF and initial decreases in the fifth minute of cardiac arrest. This trend was even more evident when a longer interval of untreated cardiac arrest was observed.18 Accordingly, progressive decreases in gasping volume and in the interval between the first and the last agonal breath are, in fact, indicators of a fatal outcome.4,5,23 In support of the beneficial effects of gasping on cerebral perfusion, we have reported previously the effects of gasping on cerebral cortical microvascular capillary blood flows.24 Gasping produced prominent increases in cerebral microcirculatory blood flow velocity and duration of flow in close relationship to the magnitude of the gasp, as measured by EtPCO2 increases. These observations indicated that gasping increases not only cerebral large vessel flow but also cerebral microvascular flow, which is the determinant of delivery of oxygen and vital substrates to the tissue. We therefore anticipate that gasping might account for better neurological outcomes. Moreover, these results further support the possibility that increases in cerebral perfusion that follow gasping may account for greater reversal of hypoxia in the brain stem. Increases in brainstem perfusion and coincident increases in gasping would make gasping an epiphenomenon.1 However, such hypotheses require additional studies to be proven. Our study was performed on young, healthy, anesthetized animals free of underlying disease, and under conditions of optimal airway control, conditions that are not likely to prevail in clinical settings. We therefore caution against direct extrapolation of the present findings to human patients. In addition pentobarbital anesthesia was used, which may have modified the frequency and pattern of gasping.25 However, gasping is also associated with greater success of resuscitation in human victims of out of hospital cardiac arrest, and therefore in the absence of anesthesia. 2,10,20
Intrathoracic pressure was not directly measured, but we employed an indirect measure, i.e. esophageal pressure. During the expiratory phase of gasping, increases in aortic pressure were greater than those in ITP; observations that are frequently reported under other settings.1,26 These greater increases in aortic pressure compared to the increases in intrathoracic pressure might be explained by the evidence that the esophageal balloon might underestimate the absolute magnitude of ITP, as demonstrated in animal models.27 Esophageal manometry, however, provides reasonable estimate of the changes in intrathoracic pressure. Differences in pressures recorded in the
Spontaneous gasping produces carotid blood flow during untreated cardiac arrest esophageal balloon closely matched the differences in ITP.26—28 These limitations notwithstanding, the present study provided further evidence of the beneficial effects of spontaneous gasping, which are associated with both ventilatory and hemodynamic effects. Gasping promotes gas exchange and circulation during cardiac arrest as observed in the increases in EtPCO2 , aortic pressure and CPP. Spontaneous gasps also produce significant increases in CBF during untreated VF. These phenomena may account for the better outcomes of CPR, observed in both animal and human victims of cardiac arrest, who presented with gasping.1,2,10,20
Conflict of interest No conflicts of interest are reported for the authors.
Acknowledgement This study was presented at the AHA Resuscitation Science Symposium 2006 and was the recipient of ‘‘Young Investigator’’ award to G.R.
References 1. Yang L, Weil MH, Noc M, Tang W, Turner T, Gazmuri RJ. Spontaneous gasping increases the ability to resuscitate during experimental cardiopulmonary resuscitation. Crit Care Med 1994;22(5):879—83. 2. Clark JJ, Larsen MP, Culley LL, Graves JR, Eisenberg MS. Incidence of agonal respirations in sudden cardiac arrest. Ann Emerg Med 1992;21(12):1464—7. 3. Tang W, Weil MH, Sun S, et al. Cardiopulmonary resuscitation by precordial compression but without mechanical ventilation. Am J Respir Crit Care Med 1994;150(6 Pt 1):1709—13. 4. Jacobi MS, Thach BT. Effect of maturation on spontaneous recovery from hypoxic apnea by gasping. J Appl Physiol 1989;66(5):2384—90. 5. Guntheroth WG, Kawabori I. Hypoxic apnea and gasping. J Clin Invest 1975;56(6):1371—7. 6. Lumsden T. Observation on the respiratory centers in the cat. J Physiol Lond 1923;57:153—60. 7. Lumsden T. Observation on the respiratory centers. J Physiol Lond 1923;57:354—67. 8. Noc M, Weil MH, Tang W, Turner T, Fukui M. Mechanical ventilation may not be essential for initial cardiopulmonary resuscitation. Chest 1995;108(3):821—7. 9. Fukui M, Weil MH, Tang W, Yang L, Sun S. Airway protection during experimental CPR. Chest 1995;108(6):1663—7. 10. Noc M, Weil MH, Sun S, Tang W, Bisera J. Spontaneous gasping during cardiopulmonary resuscitation without mechanical ventilation. Am J Respir Crit Care Med 1994;105(3):861—4.
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11. Xie J, Weil MH, Sun S, Yu T, Tang W. Spontaneous gasping generates cardiac output during cardiac arrest. Crit Care Med 2004;32(1):238—40. 12. Deshmukh HG, Weil MH, Gudipati CV, Trevino RP, Bisera J, Rackow EC. Mechanism of blood flow generated by precordial compression during CPR. I. Studies on closed chest precordial compression. Chest 1989;95(5):1092—9. 13. Gazmuri RJ, Weil MH, Von Planta M, Gazmuri RR, Shah DM, Rackow EC. Cardiac resuscitation by extracorporeal circulation after failure of conventional CPR. J Lab Clin Med 1991;118(1):65—73. 14. Gudipati CV, Weil MH, Bisera J, Deshmukh HG, Rackow EC. Expired carbon dioxide: a noninvasive monitor of cardiopulmonary resuscitation. Circulation 1988;77(1):234—9. 15. Tang W, Weil MH, Schock RB, et al. Phased chest and abdominal compression-decompression. A new option for cardiopulmonary resuscitation. Circulation 1997;95(5):1335—40. 16. Tang W, Weil MH, Sun SJ, et al. The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function. J Am Coll Cardiol 1999;34(3):815— 22. 17. Wenzel V, Linder KH, Prengel AW, Strohmenger HU. Effect of phased chest and abdominal compression—decompression cardiopulmonary resuscitation on myocardial and cerebral blood flow in pigs. Crit Care Med 2000;28(4):1107— 12. 18. Srinivasan V, Nadkarni VM, Yannopoulos D, et al. Spontaneous gasping decreases intracranial pressure and improves cerebral perfusion in a pig model of ventricular fibrillation. Resuscitation 2006;69(2):329—34. 19. Weil MH, Bisera J, Trevino RP, Rackow EC. Cardiac output and end-tidal carbon dioxide. Crit Care Med 1985;13(11):907— 9. 20. Kloss T, Roewer N, Wischhusen F. Prognosis of preclinical cardiopulmonary resuscitation. Anasth Intensivther Notfallmed 1985;20(5):237—43. 21. Eisenberg MS. Incidence and significance of gasping or agonal respirations in cardiac arrest patients. Curr Opin Crit Care 2006;12(3):204—6. 22. Rea TD. Agonal respirations during cardiac arrest. Curr Opin Crit Care 2005;11(3):188—91. 23. Jacobi MS, Gershan WM, Thach BT. Mechanism of failure of recovery from hypoxic apnea by gasping in 17- to 23-day-old mice. J Appl Physiol 1991;71(3):1098—105. 24. Ristagno G, Sun S, Huang L, et al. Gasping during cardiac arrest increases cerebral blood. Circulation 2005;12(Suppl II):1099 [Abstract]. 25. Jacobi MS, Gershan WM, Thach BT. Effect of pentobarbital on spontaneous recovery from hypoxic apnea in mice. Respir Physiol 1991;84(3):337—49. 26. Chang MW, Coffeen P, Lurie KG, Shultz J, Bache RJ, White CW. Active compression—decompression CPR improves vital organ perfusion in a dog model of ventricular fibrillation. Chest 1994;106(4):1250—9. 27. Gattinoni L, Chiumello D, Carlesso E, Valenza F. Benchto-bedside review: chest wall elastance in acute lung injury/acute respiratory distress syndrome patients. Crit Care 2004;8(5):350—5. 28. Naughton MT, Rahman MA, Hara K, Floras JS, Bradley TD. Effect of continuous positive airway pressure on intrathoracic and left ventricular transmural pressures in patients with congestive heart failure. Circulation 1995;91(6):1725—31.
EXPERIMENTAL PAPER
Spontaneous gasping produces carotid blood flow during untreated cardiac arrest夽 Giuseppe Ristagno a, Wanchun Tang a,b,∗, Shijie Sun a,b, Max Harry Weil a,b,c a
Weil Institute of Critical Care Medicine, Rancho Mirage, CA, United States Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States c Northwestern University, Feinberg School of Medicine, Chicago, IL, United States b
Received 25 January 2007 ; received in revised form 13 April 2007; accepted 19 April 2007 KEYWORDS Cardiac arrest; Gasping; Carotid blood flow; Intrathoracic pressure
Summary Objectives: Coincident with ‘‘agonal’’ gasping during cardiac arrest, there are prominent increases in stroke volumes even in the absence of chest compression. In the present study, we tested the hypothesis that gasps also increase carotid blood flow (CBF) during untreated cardiac arrest. Materials and methods: The tracheas of nine domestic male pigs, weighing 39 ± 2 kg, were intubated and animals were ventilated mechanically. Ventricular fibrillation (VF) was induced electrically and untreated for 5 min. Coincident with the onset of VF, mechanical ventilation was discontinued. The right femoral artery and vein were cannulated. Intrathoracic pressure (ITP) was measured with the aid of a balloon tipped catheter advanced into the esophagus for a distance of 35 cm. A transonic flowprobe was placed around the right common carotid artery for measurement of CBF. Results: Gasps increased in frequency during the first 4 min of untreated VF together with increases in CBF. The CBF produced by gasping averaged 220 ± 102 mL/min, which represented approximately 59% of a pre-cardiac arrest CBF. Significant increases in CBF were highly correlated with the decreases in ITP during the inspiratory phase of the gaspings (r = 0.78) and with the increases in aortic pressure during the expiratory phase of the gaspings (r = 0.76). Conclusions: Spontaneous gasps produce significant increases in CBF during untreated cardiac arrest. The present study therefore confirmed beneficial effects of gasping during cardiac arrest. © 2007 Elsevier Ireland Ltd. All rights reserved.
夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at 10.1016/j.resuscitation.2007.04.020. ∗ Corresponding author at: Weil Institute of Critical Care Medicine, 35100 Bob Hope Drive, Rancho Mirage, CA 92270, United States. Tel.: +1 760 778 4911; fax: +1 760 778 3468. E-mail address: [email protected] (W. Tang).
0300-9572/$ — see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.resuscitation.2007.04.020
Spontaneous gasping produces carotid blood flow during untreated cardiac arrest
Introduction Gasping is a striking ‘‘agonal’’ respiratory phenomenon characterized by forceful inspirations, which are often observed in the dramatic conditions of sudden cardiac arrest.1,2 In both experimental and clinical reports the presence and the frequency of gasping were predictive of the success of resuscitation.2,3 Accordingly, gasping is considered an ‘‘autoresuscitative’’ phenomenon triggered by hypoxia,4,5 which persists until respiratory centers located in the caudal portion of the medulla oblongata are disabled.6,7 In experimental models of induced apnea, gasping appeared after an interval of approximately 2 min, when the arterial oxygen tension (PaO2 ) decreased below 5 mmHg. This agonal breathing was able to improve PaO2 to over 30 mmHg promptly and thereby resuming regular respiration.5 Gasping promotes entry of the air into the lungs, securing greater oxygen and CO2 exchange. In a porcine model of cardiac arrest, spontaneous gasping was able to generate more than 4 L/min of ventilation.8 Moreover, gasping has been shown to provide another and probably important source of pulmonary gas exchange during CPR.8—10 More frequent gaspings accounted for greater PaO2 and lower arterial CO2 tensions, when precordial compression, combined with oxygen supplied at the port of the tracheal tube, was the only resuscitative intervention.10 We have documented previously the hemodynamic effects of gasping during untreated cardiac arrest. The expiratory phase of gasping is associated with increases in arterial pressure and in coronary perfusion pressure (CPP).1 Nevertheless, earlier reports have demonstrated that gasping improves not only ventilation but generates cardiac output during untreated cardiac arrest.10,11 Based on the favourable hemodynamic effects which follow each gasp, we therefore previously anticipated that gasping would facilitate increased cerebral perfusion.1 In the present study we investigated the effects of gasping on generation of carotid blood flow (CBF). We hypothesized that gasping would be able to produce increases in CBF during untreated cardiac arrest.
Materials and methods The experiments were performed in an established porcine model of cardiac arrest.12—14 All animals
367
received humane care in compliance with the ‘‘Principles of Laboratory Animal Care’’ formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH publication 86—32, revised 1985). The protocol was approved by the Institutional Animal Care and Use Committee of the Weil Institute of Critical Care Medicine. The animal laboratories of the Institute are fully accredited by American Association for Accreditation of Laboratory Animal Care (AAALAC) International. Nine Yorkshire-cross male domestic pigs (Sus scrofa) weighing 39 ± 2 kg were fasted overnight except for free access to water. Anesthesia was initiated by intramuscular injection of ketamine (20 mg/kg) and completed by ear vein injection of sodium pentobarbital (30 mg/kg). Additional doses of sodium pentobarbital (8 mg/kg) were injected at intervals of approximately 1 h to maintain anesthesia. A cuffed tracheal tube was advanced into the trachea and animals were mechanically ventilated with a volume-controlled ventilator (Model MA-1, Puritan-Bennett, Carlsbad, CA), with a tidal volume of 15 mL/kg, peak flow of 40 L/min, and FiO2 of 0.21. End-tidal PCO2 (EtPCO2 ) was monitored with an infrared capnometer (Model NPB-75, Nellcor Puritan Bennett Inc., Pleasanton, CA). Respiratory frequency was adjusted to maintain EtPCO2 between 35 and 40 mmHg. For measurement of mean aortic pressure (MAP), a fluid filled 8-Fr angiographic catheter (model 6523; USCI C.R. Bard, Inc., Salt Lake City, UT) was advanced from the right femoral artery into the thoracic aorta. For the measurements of right atrial pressure (RAP) a 7-Fr balloon tipped catheter (Abbott Critical Care 41216) with an atrial port was advanced from the right femoral vein and flow directed into pulmonary artery. Conventional external pressure transducers were used (Transpac IV, Abbott Critical Care Systems, North Chicago, IL). For measurement of intrathoracic pressure (ITP) a balloon tipped catheter, connected to a pressure transducer, was advanced from the incisor teeth into the esophagus for a distance of 35 cm.15 CBF was measured continuously with the aid of a flowprobe (Ultrasonic Blood Flow Meter, T101, Transonic Systems Inc., Ithaca, NY) positioned around the right common carotid artery. To induce VF, a 5-Fr pacing catheter (EP Technologies, Inc., Mountain View, CA) was advanced from the surgically exposed right cephalic vein into the right ventricle. The catheter subsequently was advanced into the apex of the right ventricle with the aid of an image intensifier. To measure the scalar
368
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electrocardiogram, three adhesive electrodes were applied to the shaved skin of the right and left infraclavicular areas and the left lower abdomen. Cardiac arrest was induced with 1 mA alternating current delivered to the endocardium of the right ventricle. After onset of VF, the pacing catheter was removed and mechanical ventilation was discontinued. VF was maintained for 5 min without any intervention, except for the tracheal tube that was maintained in position. Hemodynamic data, CBF, EtPCO2 , ITP and ECG were continuously measured and recorded on a PCbased data acquisition system supported by CODAS hardware/software as previously described.16 CPP was digitally computed from the differences in time-coincident diastolic aortic and right atrial pressures and displayed in real time.
Statistical analyses All data are presented as mean ± S.D. For comparisons between time-based measurements within the groups, analysis of variance was used for repeated measurements. Linear correlations were calculated using the Pearson correlation coefficient. A p value < 0.05 was regarded as statistically significant.
Results All the animals presented with gasping during the 5 min interval of untreated cardiac arrest and gasping followed a crescendo—decrescendo pattern. Over the 5 min interval of untreated VF, gaspings increased CBF together with aortic pressure and EtPCO2 , and decreased right atrial pressures, as shown in Figure 1. The inspiratory phase of gasping was characterized by significant decreases in ITP which were accompanied by corresponding decreases of pressures in the aorta and right atrium. Following the expiratory phase, significant increases in aortic, right atrial and CPP were observed (p < 0.0001), together with increases in EtPCO2 (p < 0.0001), as detailed in Table 1. Gasping significantly increased in frequency over the minutes of untreated cardiac arrest, from 0 during the first min to 7 during the fourth minute (Figure 2). Such increases in the frequency of gasping were accompanied by significantly greater decreases in ITP during the inspiratory phase of gasping (p < 0.01) and significantly greater increases in aortic pressure during the expiratory phase of gasping (p < 0.01), as shown in Figure 3.
Figure 1 Effects of gasping on CBF, aortic and right atrial pressures and EtPCO2 during 5 min interval of untreated VF.
CBF produced by each gasp, significantly increased over the period of untreated VF (Figure 4), from 119 ± 59 mL/min during the second min of VF to 224 ± 111 mL/min in the fifth minute of VF (p < 0.01). Over the 5 min interval of untreated cardiac arrest, CBF generated by gasping averaged 220 ± 102 mL/min. These values represented approximately 59% of the CBF generated from the beating heart, which was 367 ± 64 mL/min (p < 0.01).
Figure 2 Increases in frequency of gaspings over 5 min interval of untreated VF *p < 0.05 and **p < 0.01 vs. VF 2 min; † p < 0.01 vs. VF 1 min.
Spontaneous gasping produces carotid blood flow during untreated cardiac arrest
369
Table 1 Effects of inspiratory and expiratory phases of gasping on aortic, right atrial, coronary perfusion and intrathoracic pressures and end-tidal PCO2 during untreated VF Gasping
Prior to gasping
Aortic pressure (mmHg) Right atrial pressure (mmHg) Coronary perfusion pressure (mmHg) Intrathoracic pressure (mmHg) End-tidal PCO2 (mmHg)
20 16 3 2 1
± ± ± ± ±
Inspiration −1 1 −2 −20 1
3 4 3 3 1
± ± ± ± ±
15* 8* 14 15* 1
Expiration 39 29 10 10 13
± ± ± ± ±
8† 4† 8† 6† 3†
*p < 0.0001 vs. ‘‘prior to gasping’’. † p < 0.0001 vs. ‘‘prior to gasping’’ and ‘‘inspiration’’.
Figure 3 Increases in CBF produced by gasps over 5 min interval of untreated VF. *p < 0.01 vs. VF 2 min; † p < 0.05 vs. VF 3 min.
Figure 5 Linear correlation between CBF generated by gasping with decreases in ITP during the inspiratory phase of gasping and with increases in aortic pressure generated during the expiratory phase of gasping.
Increases in CBF generated by gasping were highly correlated with the decreases in ITP (r = 0.78, p < 0.01) observed during the inspiration phase of the gasping and with the increases in aortic pressure (r = 0.76, p < 0.01) during the expiratory phase of gasping (Figure 5).
Discussion
Figure 4 Effects of gasping on ITP and aortic pressure during 5 min interval of untreated VF. Decreases in ITP and increases in aortic pressure followed each gasping. § p < 0.01 vs. VF 1 min; *p < 0.01 vs. VF 2 min and VF 5 min; † p < 0.05 vs. VF 2 min.
Gasping began after the first min of cardiac arrest and increased in frequency during the first 4 min of untreated VF together with increases in CBF. The CBF generated by gasping averaged approximately 59% of pre-cardiac arrest CBF. These significant increases in CBF were highly correlated with the decreases in ITP observed during the inspiratory phase of the gasping and with the increases in aortic pressure that typically followed the expiratory phase of the gasping.
370 Generation of CBF by gasping is explained by the hemodynamic effects that followed each gasp. During the inspiratory phase, forceful contraction of inspiratory muscles produced decreases in ITP of more than 20 mmHg and thereby favoured the venous return to the heart and ultimately to the preload.17 Such decreases in ITP were, in fact, accompanied by decreases in right atrial pressure of more than 15 mmHg, generating therefore a pressure gradient between the peripheral veins and the right atrium. Following the expiratory phase of the gasping, we observed increases in ITP that were accompanied by increases in aortic pressure of more than 38 mmHg, which were greater than increases in right atrial pressure and thereby accounted for increases in CPP. Moreover, it has recently been reported that spontaneous gasping during cardiac arrest produces significant decreases in intra-cranial pressure, which averaged 7 mmHg, along with significant increases in cerebral perfusion pressure, of approximately 11 mmHg.18 These mechanisms might also account for the generation of CBF during gasping. The present findings confirm previous observations of beneficial effects of gasping. Increases in aortic pressure and CPP have been shown to be highly related with stroke volumes generated by gasping. During its expiratory phase in fact gasping generates stroke volumes that are approximately 60% of the spontaneously beating heart.11 Increases in EtPCO2 coincident with each gasp also reflect increases in pulmonary blood flow and therefore increases in cardiac output.19 In our study such increases in EtCO2 were confirmed and the CBF produced by gasping was approximately 59% of the pre-arrest flow, values which are consistent with previously reported amounts of echocardiographically measured stroke volumes produced by gasping.11 In clinical settings, presence of gasping has also been associated with successful resuscitation and increased survival.2,20,21 Agonal respiration has been reported in human victims of cardiac arrest with an incidence of more than 55% of witnessed sudden deaths.21 In 445 instances of sudden death, agonal respirations had been reported in 40% of the victims; 27% of patients who presented with gasping were successfully discharged from the hospital, compared with only 9% of the patients who did not gasp.2 Gasps have been associated with witnessed events, VF, and survival, suggesting that agonal respiration is a marker of an arrest’s early phase.22 This is consistent with our report in which a crescendo—decrescendo pattern was observed, with gradual increases of the hemodynamic effects
G. Ristagno et al. of the gasping over the initial 4 min of VF and initial decreases in the fifth minute of cardiac arrest. This trend was even more evident when a longer interval of untreated cardiac arrest was observed.18 Accordingly, progressive decreases in gasping volume and in the interval between the first and the last agonal breath are, in fact, indicators of a fatal outcome.4,5,23 In support of the beneficial effects of gasping on cerebral perfusion, we have reported previously the effects of gasping on cerebral cortical microvascular capillary blood flows.24 Gasping produced prominent increases in cerebral microcirculatory blood flow velocity and duration of flow in close relationship to the magnitude of the gasp, as measured by EtPCO2 increases. These observations indicated that gasping increases not only cerebral large vessel flow but also cerebral microvascular flow, which is the determinant of delivery of oxygen and vital substrates to the tissue. We therefore anticipate that gasping might account for better neurological outcomes. Moreover, these results further support the possibility that increases in cerebral perfusion that follow gasping may account for greater reversal of hypoxia in the brain stem. Increases in brainstem perfusion and coincident increases in gasping would make gasping an epiphenomenon.1 However, such hypotheses require additional studies to be proven. Our study was performed on young, healthy, anesthetized animals free of underlying disease, and under conditions of optimal airway control, conditions that are not likely to prevail in clinical settings. We therefore caution against direct extrapolation of the present findings to human patients. In addition pentobarbital anesthesia was used, which may have modified the frequency and pattern of gasping.25 However, gasping is also associated with greater success of resuscitation in human victims of out of hospital cardiac arrest, and therefore in the absence of anesthesia. 2,10,20
Intrathoracic pressure was not directly measured, but we employed an indirect measure, i.e. esophageal pressure. During the expiratory phase of gasping, increases in aortic pressure were greater than those in ITP; observations that are frequently reported under other settings.1,26 These greater increases in aortic pressure compared to the increases in intrathoracic pressure might be explained by the evidence that the esophageal balloon might underestimate the absolute magnitude of ITP, as demonstrated in animal models.27 Esophageal manometry, however, provides reasonable estimate of the changes in intrathoracic pressure. Differences in pressures recorded in the
Spontaneous gasping produces carotid blood flow during untreated cardiac arrest esophageal balloon closely matched the differences in ITP.26—28 These limitations notwithstanding, the present study provided further evidence of the beneficial effects of spontaneous gasping, which are associated with both ventilatory and hemodynamic effects. Gasping promotes gas exchange and circulation during cardiac arrest as observed in the increases in EtPCO2 , aortic pressure and CPP. Spontaneous gasps also produce significant increases in CBF during untreated VF. These phenomena may account for the better outcomes of CPR, observed in both animal and human victims of cardiac arrest, who presented with gasping.1,2,10,20
Conflict of interest No conflicts of interest are reported for the authors.
Acknowledgement This study was presented at the AHA Resuscitation Science Symposium 2006 and was the recipient of ‘‘Young Investigator’’ award to G.R.
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