CASE CONFERENCES The Clinical Physiologist Section Editor: John Kreit, M.D.
Systolic Blood Pressure Variation during Mechanical Ventilation John W. Kreit Department of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Keywords: mechanical ventilation; blood pressure; hemodynamics
In Brief Shortly after admission to an intensive care unit from the emergency department, an elderly man was intubated for management of respiratory failure precipitated by multifocal pneumonia and septic shock. Arterial blood pressure monitoring disclosed marked variations in systolic blood pressure associated with the ventilator cycle. The blood pressure variations resolved in response to a medical intervention that derived from knowledge of the physiological effect of positive pressure mechanical ventilation on intrathoracic hemodynamics.
The Clinical Challenge A 76-year-old man presented to the emergency department (ED) with several days of fever, chills, productive cough, and dyspnea. On examination, the patient appeared uncomfortable and was breathing rapidly. The blood pressure was 74/40 mm Hg, the pulse was 126 beats/min, and the respiratory rate was 36 breaths/min. The arterial oxygen saturation was 82% measured by pulse oximetry while the patient breathed ambient air. Crackles, bronchial breath sounds, and egophony were heard over the lower lobes of both lungs. The remainder of the physical examination was unremarkable. A chest radiograph demonstrated extensive, bilateral consolidation. The white blood cell count was 28.6 3 109/L, the Hb
concentration was 15.2 g/dl, the blood serum level of creatinine was 1.9 mg/dl, the blood urea nitrogen was 59 mg/dl, the total CO2 was 18.6 mmol/L, and the lactate was 4.6 mmol/L. Other routine blood studies were unremarkable. The patient was given intravenous normal saline, norepinephrine, and broadspectrum antibiotics. He was admitted to the medical intensive care unit (MICU) with the diagnoses of pneumonia and septic shock. Shortly after arrival in the MICU, the patient required intubation because of increasing respiratory distress. A central venous catheter and an arterial catheter were inserted. While the patient was heavily sedated and not making spontaneous respiratory efforts, marked ventilationrelated changes in systolic blood pressure were noted (Figure 1).
Questions How does mechanical ventilation alter systemic hemodynamic pressures?
What is the clinical significance of the noted variation in systolic blood pressure? What modifications in mechanical ventilation and hemodynamic support are indicated to address the marked variations in systolic blood pressure?
Clinical Reasoning All intrathoracic structures are exposed to pleural pressure (PPL). At end-expiration, PPL is normally slightly negative relative to atmospheric pressure. During a passive, mechanical, positive-pressure breath, PPL increases as the lungs are forced outward against the chest wall. This increases the pressure within the superior vena cava and right atrium, which reduces the pressure gradient driving blood flow from the extrathoracic veins. The drop in venous return causes right ventricular preload and stroke volume to fall, which, after several cardiac cycles, decreases left ventricular preload and stroke volume. During passive
Figure 1. Ventilation-related changes in systolic blood pressure are evident during passive mechanical ventilation.
(Received in original form December 11, 2013; accepted in final form January 3, 2014 ) Correspondence and requests for reprints should be addressed to John W. Kreit, M.D., University of Pittsburgh, Pulmonary, Allergy, and Critical Care Medicine, 628 NW UPMC-Montefiore, 3459 Fifth Avenue, Pittsburgh, Pennsylvania 15213. E-mail: [email protected] Ann Am Thorac Soc Vol 11, No 3, pp 462–465, Mar 2014 Copyright © 2014 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201312-439CC Internet address: www.atsjournals.org
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AnnalsATS Volume 11 Number 3 | March 2014
CASE CONFERENCES expiration, PPL falls, and venous return and left ventricular preload and stroke volume increase. When left ventricular preload has been optimized and the left ventricle is functioning on the plateau portion of the ventricular function (Starling) curve, cyclical ventilation-related changes in venous return and left ventricular preload generally have little effect on left ventricular stroke volume and systolic blood pressure. When left ventricular preload is low, however, the heart is functioning on the steep portion of the curve, and the drop in venous return during mechanical inflation is sufficient to significantly reduce left ventricular stroke volume and systolic blood pressure. Thus, marked ventilation-related variation in systolic blood pressure in passively ventilated patients is a marker of inadequate left ventricular preload and predicts hemodynamic improvement with volume loading (i.e., volume responsiveness). Based on this reasoning, the patient’s physicians concluded that this man had received inadequate volume resuscitation to overcome preadmission dehydration and sepsis-related intravascular volume loss and vasodilation.
Figure 2. Ventilation-related changes in systolic blood pressure have resolved after volume resuscitation.
A mechanical breath directly inflates the lungs. As volume increases, the outward recoil of the chest wall decreases and PPL progressively rises. Pleural pressure becomes positive (supra-atmospheric) once the chest wall exceeds its equilibrium volume, and its elastic recoil is directed inward against the inflating lungs. Passive expiration is accompanied by the return of PPL to its baseline level. The Effect of Pleural Pressure on Intramural and Transmural Pressure
Because the visceral pleura surrounds both lungs and the parietal pleura lines the chest wall, mediastinum, and diaphragm, everything in the thorax is constantly exposed to pleural pressure. This means that PPL is, for practical purposes, the pressure
outside the heart and the intrathoracic arteries and veins. Pleural pressure also alters the pressure inside each of these structures in proportion to its compliance. That is, the thinner and less rigid the walls of the blood vessel or heart chamber (i.e., the higher its compliance), the greater the effect of PPL on intramural pressure (PIM). It follows that PPL also influences transmural pressure (PTM), which is the gradient between the inside and the outside of these intrathoracic structures. These concepts are illustrated in Figure 4. An increase in PPL causes a similar rise in the pressure within relatively thinwalled structures, such as the superior vena cava, right atrium, and pulmonary arteries and veins. Notice that the large change in PIM causes a relatively small drop in PTM.
The Clinical Solution Within 3 hours of admission to the MICU, the patient received 4 L of normal saline. His norepinephrine requirement fell from 1.0 to 0.06 mg/kg/min, and the ventilationrelated changes in systolic blood pressure resolved (Figure 2).
The Science behind the Solution The Effect of Mechanical Ventilation on Pleural Pressure
The change in PPL during a positivepressure, mechanical breath is shown in the upper panel of Figure 3. At the end of a passive expiration, the inward elastic recoil of the lungs is exactly balanced by the outward recoil of the chest wall. These opposing forces cause the pressure in the potential space between the visceral and parietal pleura to fall below atmospheric pressure (PATM). Because all pressures are referenced to it, PATM is considered to be zero, and mean end-expiratory PPL is normally negative.
Figure 3. The change in airway (PAW), alveolar (PALV), and pleural (PPL) pressure, flow, and volume during a mechanical breath.
Case Conferences: The Clinical Physiologist
463
CASE CONFERENCES d
d
d
Figure 4. The effect of increasing pleural pressure (PPL) from 23 to 12 on the diameter and intramural (PIM) and transmural pressure (PTM) of a compliant intrathoracic structure. PTM = PIM – PPL.
The Importance of Intramural and Transmural Pressure Intramural pressure regulates blood flow. The rate at which blood moves: from
one region of the body to another (V) is
directly related to the intramural pressure gradient (DPIM) and inversely proportional to vascular resistance (R). $ (1) V ¼ DPIM =R Transmural pressure regulates vascular volume. Because it is the difference between
internal and external pressure, PTM is the distending pressure of the blood vessels and heart chambers. It follows that a change in PTM alters the volume (DV) of a vascular structure in proportion to its compliance (C). DV ¼ DPTM 3 C
(2)
As shown in Figure 4, even a small change in PTM has a significant effect on vascular volume when compliance is high. Recall that vascular resistance is inversely related to the fourth or fifth power of the vessel radius, depending on whether flow is laminar or turbulent. Thus, any decrease in vascular volume (i.e., radius) significantly increases vascular resistance, which reduces blood flow (see Equation 1). The Hemodynamic Effects of Mechanical Ventilation
Based on the concepts discussed above, the changes in PPL that accompany mechanical ventilation have predictable effects on cardiovascular function (Figure 5). d
Figure 5. Schematic representation of the changes in pleural pressure (PPL), right atrial pressure (PRA), venous return, left ventricular (LV) stroke volume, and systolic blood pressure (SBP) during a mechanical breath. Exp = expiration; Insp = inspiration.
464
d
The pressure within the superior vena cava, right atrium, and pulmonary arteries and veins rises and PTM falls, which increases resistance.
d
The decrease in the pressure gradient between the extrathoracic veins and the superior vena cava and right atrium and the increase in vascular resistance reduces venous return. The fall in venous return reduces right ventricular preload and stroke volume. The drop in the PTM of the pulmonary veins reduces vascular volume and forces blood into the left atrium. Left ventricular preload and stroke volume initially rise. + More blood enters the left ventricule from the pulmonary veins. + Because total ventricular volume is limited by the pericardium, as right ventricular preload and size decrease, the left ventricule enlarges and intraventricular pressure falls, which improves diastolic filling. After several cardiac cycles, left ventricular preload and stroke volume fall with the decrease in blood ejected by the right ventricle.
Because of the initial rise in left ventricular preload and stroke volume, blood pressure may increase early in inspiration but then falls with the drop in left ventricular stroke volume (Figure 6). During passive expiration, PIM, PTM, vascular size and resistance, and ventricular volume, preload, and stroke volume return to baseline. Predicting Volume Responsiveness
The degree to which systolic blood pressure changes with the normal ventilation-related variation in PPL may be used to assess left ventricular preload and predict the response to volume loading. This can be understood by examining a normal ventricular function (Starling) curve (Figure 7). If the heart is functioning on the relatively flat portion of the curve, the drop in left ventricular preload produced by mechanical inflation will have little effect on stroke volume and systolic blood pressure. Giving additional
Figure 6. The variation in arterial blood pressure during a mechanical breath.
AnnalsATS Volume 11 Number 3 | March 2014
CASE CONFERENCES
Figure 7. When left ventricular end-diastolic volume and stroke volume occupy a point on the ascending portion of the ventricular function curve, the drop in left ventricular preload produced by a mechanical breath (dashed line) causes a relatively large fall in stroke volume (A → B). When ventricular preload is high, the fall in left ventricular end-diastolic volume has little effect on stroke volume (C → D). (Modified with permission from Rice TB, Gingo M, Kreit JW. Mechanical ventilation and the cardiovascular system. In: Kreit JW, editor. Mechanical ventilation, 1st ed. New York: Oxford University Press; 2012. pp. 111–126.)
intravascular volume to such patients would not be expected to improve hemodynamics. If, on the other hand, left ventricular preload is inadequate and the
heart is functioning on the ascending portion of the curve, the same decrease in preload will have a much greater hemodynamic effect. Thus, a large
Recommended Reading Fessler HE. Heart-lung interactions: applications in the critically ill. Eur Resp J 1997;10:226–237. Magder S. Clinical usefulness of respiratory variations in arterial pressure. Am J Resp Crit Care Med 2004;169:151–155.
Case Conferences: The Clinical Physiologist
ventilation-related change in systolic blood pressure predicts that volume loading will significantly increase stroke volume and blood pressure. The link between mechanical ventilation–induced systolic blood pressure variation and volume responsiveness exists only during passive mechanical ventilation. This is because inspiratory and expiratory efforts generate pleural pressure swings that may produce systolic blood pressure variation even in patients with optimal left ventricular preload. For the same reason, systolic blood pressure variation during spontaneous breathing is also a poor predictor of volume responsiveness. Although several investigators have attempted to quantify the change in systolic blood pressure that separates volume responders from nonresponders during passive mechanical ventilation, these results are difficult to generalize because of differences in ventilator settings and study populations. n Author disclosures are available with the text of this article at www.atsjournals.org.
Perel A. The physiological basis of arterial pressure variation during positive-pressure ventilation. Reanimation 2005;14:162–171. Feihl F, Broccard AF. Interactions between respiration and systemic hemodynamics. Part 1. Intensive Care Med 2009;35:45–54. Feihl F, Broccard AF. Interactions between respiration and systemic hemodynamics. Part 2. Intensive Care Med 2009;35:198–205.
465
Systolic Blood Pressure Variation during Mechanical Ventilation John W. Kreit Department of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Keywords: mechanical ventilation; blood pressure; hemodynamics
In Brief Shortly after admission to an intensive care unit from the emergency department, an elderly man was intubated for management of respiratory failure precipitated by multifocal pneumonia and septic shock. Arterial blood pressure monitoring disclosed marked variations in systolic blood pressure associated with the ventilator cycle. The blood pressure variations resolved in response to a medical intervention that derived from knowledge of the physiological effect of positive pressure mechanical ventilation on intrathoracic hemodynamics.
The Clinical Challenge A 76-year-old man presented to the emergency department (ED) with several days of fever, chills, productive cough, and dyspnea. On examination, the patient appeared uncomfortable and was breathing rapidly. The blood pressure was 74/40 mm Hg, the pulse was 126 beats/min, and the respiratory rate was 36 breaths/min. The arterial oxygen saturation was 82% measured by pulse oximetry while the patient breathed ambient air. Crackles, bronchial breath sounds, and egophony were heard over the lower lobes of both lungs. The remainder of the physical examination was unremarkable. A chest radiograph demonstrated extensive, bilateral consolidation. The white blood cell count was 28.6 3 109/L, the Hb
concentration was 15.2 g/dl, the blood serum level of creatinine was 1.9 mg/dl, the blood urea nitrogen was 59 mg/dl, the total CO2 was 18.6 mmol/L, and the lactate was 4.6 mmol/L. Other routine blood studies were unremarkable. The patient was given intravenous normal saline, norepinephrine, and broadspectrum antibiotics. He was admitted to the medical intensive care unit (MICU) with the diagnoses of pneumonia and septic shock. Shortly after arrival in the MICU, the patient required intubation because of increasing respiratory distress. A central venous catheter and an arterial catheter were inserted. While the patient was heavily sedated and not making spontaneous respiratory efforts, marked ventilationrelated changes in systolic blood pressure were noted (Figure 1).
Questions How does mechanical ventilation alter systemic hemodynamic pressures?
What is the clinical significance of the noted variation in systolic blood pressure? What modifications in mechanical ventilation and hemodynamic support are indicated to address the marked variations in systolic blood pressure?
Clinical Reasoning All intrathoracic structures are exposed to pleural pressure (PPL). At end-expiration, PPL is normally slightly negative relative to atmospheric pressure. During a passive, mechanical, positive-pressure breath, PPL increases as the lungs are forced outward against the chest wall. This increases the pressure within the superior vena cava and right atrium, which reduces the pressure gradient driving blood flow from the extrathoracic veins. The drop in venous return causes right ventricular preload and stroke volume to fall, which, after several cardiac cycles, decreases left ventricular preload and stroke volume. During passive
Figure 1. Ventilation-related changes in systolic blood pressure are evident during passive mechanical ventilation.
(Received in original form December 11, 2013; accepted in final form January 3, 2014 ) Correspondence and requests for reprints should be addressed to John W. Kreit, M.D., University of Pittsburgh, Pulmonary, Allergy, and Critical Care Medicine, 628 NW UPMC-Montefiore, 3459 Fifth Avenue, Pittsburgh, Pennsylvania 15213. E-mail: [email protected] Ann Am Thorac Soc Vol 11, No 3, pp 462–465, Mar 2014 Copyright © 2014 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201312-439CC Internet address: www.atsjournals.org
462
AnnalsATS Volume 11 Number 3 | March 2014
CASE CONFERENCES expiration, PPL falls, and venous return and left ventricular preload and stroke volume increase. When left ventricular preload has been optimized and the left ventricle is functioning on the plateau portion of the ventricular function (Starling) curve, cyclical ventilation-related changes in venous return and left ventricular preload generally have little effect on left ventricular stroke volume and systolic blood pressure. When left ventricular preload is low, however, the heart is functioning on the steep portion of the curve, and the drop in venous return during mechanical inflation is sufficient to significantly reduce left ventricular stroke volume and systolic blood pressure. Thus, marked ventilation-related variation in systolic blood pressure in passively ventilated patients is a marker of inadequate left ventricular preload and predicts hemodynamic improvement with volume loading (i.e., volume responsiveness). Based on this reasoning, the patient’s physicians concluded that this man had received inadequate volume resuscitation to overcome preadmission dehydration and sepsis-related intravascular volume loss and vasodilation.
Figure 2. Ventilation-related changes in systolic blood pressure have resolved after volume resuscitation.
A mechanical breath directly inflates the lungs. As volume increases, the outward recoil of the chest wall decreases and PPL progressively rises. Pleural pressure becomes positive (supra-atmospheric) once the chest wall exceeds its equilibrium volume, and its elastic recoil is directed inward against the inflating lungs. Passive expiration is accompanied by the return of PPL to its baseline level. The Effect of Pleural Pressure on Intramural and Transmural Pressure
Because the visceral pleura surrounds both lungs and the parietal pleura lines the chest wall, mediastinum, and diaphragm, everything in the thorax is constantly exposed to pleural pressure. This means that PPL is, for practical purposes, the pressure
outside the heart and the intrathoracic arteries and veins. Pleural pressure also alters the pressure inside each of these structures in proportion to its compliance. That is, the thinner and less rigid the walls of the blood vessel or heart chamber (i.e., the higher its compliance), the greater the effect of PPL on intramural pressure (PIM). It follows that PPL also influences transmural pressure (PTM), which is the gradient between the inside and the outside of these intrathoracic structures. These concepts are illustrated in Figure 4. An increase in PPL causes a similar rise in the pressure within relatively thinwalled structures, such as the superior vena cava, right atrium, and pulmonary arteries and veins. Notice that the large change in PIM causes a relatively small drop in PTM.
The Clinical Solution Within 3 hours of admission to the MICU, the patient received 4 L of normal saline. His norepinephrine requirement fell from 1.0 to 0.06 mg/kg/min, and the ventilationrelated changes in systolic blood pressure resolved (Figure 2).
The Science behind the Solution The Effect of Mechanical Ventilation on Pleural Pressure
The change in PPL during a positivepressure, mechanical breath is shown in the upper panel of Figure 3. At the end of a passive expiration, the inward elastic recoil of the lungs is exactly balanced by the outward recoil of the chest wall. These opposing forces cause the pressure in the potential space between the visceral and parietal pleura to fall below atmospheric pressure (PATM). Because all pressures are referenced to it, PATM is considered to be zero, and mean end-expiratory PPL is normally negative.
Figure 3. The change in airway (PAW), alveolar (PALV), and pleural (PPL) pressure, flow, and volume during a mechanical breath.
Case Conferences: The Clinical Physiologist
463
CASE CONFERENCES d
d
d
Figure 4. The effect of increasing pleural pressure (PPL) from 23 to 12 on the diameter and intramural (PIM) and transmural pressure (PTM) of a compliant intrathoracic structure. PTM = PIM – PPL.
The Importance of Intramural and Transmural Pressure Intramural pressure regulates blood flow. The rate at which blood moves: from
one region of the body to another (V) is
directly related to the intramural pressure gradient (DPIM) and inversely proportional to vascular resistance (R). $ (1) V ¼ DPIM =R Transmural pressure regulates vascular volume. Because it is the difference between
internal and external pressure, PTM is the distending pressure of the blood vessels and heart chambers. It follows that a change in PTM alters the volume (DV) of a vascular structure in proportion to its compliance (C). DV ¼ DPTM 3 C
(2)
As shown in Figure 4, even a small change in PTM has a significant effect on vascular volume when compliance is high. Recall that vascular resistance is inversely related to the fourth or fifth power of the vessel radius, depending on whether flow is laminar or turbulent. Thus, any decrease in vascular volume (i.e., radius) significantly increases vascular resistance, which reduces blood flow (see Equation 1). The Hemodynamic Effects of Mechanical Ventilation
Based on the concepts discussed above, the changes in PPL that accompany mechanical ventilation have predictable effects on cardiovascular function (Figure 5). d
Figure 5. Schematic representation of the changes in pleural pressure (PPL), right atrial pressure (PRA), venous return, left ventricular (LV) stroke volume, and systolic blood pressure (SBP) during a mechanical breath. Exp = expiration; Insp = inspiration.
464
d
The pressure within the superior vena cava, right atrium, and pulmonary arteries and veins rises and PTM falls, which increases resistance.
d
The decrease in the pressure gradient between the extrathoracic veins and the superior vena cava and right atrium and the increase in vascular resistance reduces venous return. The fall in venous return reduces right ventricular preload and stroke volume. The drop in the PTM of the pulmonary veins reduces vascular volume and forces blood into the left atrium. Left ventricular preload and stroke volume initially rise. + More blood enters the left ventricule from the pulmonary veins. + Because total ventricular volume is limited by the pericardium, as right ventricular preload and size decrease, the left ventricule enlarges and intraventricular pressure falls, which improves diastolic filling. After several cardiac cycles, left ventricular preload and stroke volume fall with the decrease in blood ejected by the right ventricle.
Because of the initial rise in left ventricular preload and stroke volume, blood pressure may increase early in inspiration but then falls with the drop in left ventricular stroke volume (Figure 6). During passive expiration, PIM, PTM, vascular size and resistance, and ventricular volume, preload, and stroke volume return to baseline. Predicting Volume Responsiveness
The degree to which systolic blood pressure changes with the normal ventilation-related variation in PPL may be used to assess left ventricular preload and predict the response to volume loading. This can be understood by examining a normal ventricular function (Starling) curve (Figure 7). If the heart is functioning on the relatively flat portion of the curve, the drop in left ventricular preload produced by mechanical inflation will have little effect on stroke volume and systolic blood pressure. Giving additional
Figure 6. The variation in arterial blood pressure during a mechanical breath.
AnnalsATS Volume 11 Number 3 | March 2014
CASE CONFERENCES
Figure 7. When left ventricular end-diastolic volume and stroke volume occupy a point on the ascending portion of the ventricular function curve, the drop in left ventricular preload produced by a mechanical breath (dashed line) causes a relatively large fall in stroke volume (A → B). When ventricular preload is high, the fall in left ventricular end-diastolic volume has little effect on stroke volume (C → D). (Modified with permission from Rice TB, Gingo M, Kreit JW. Mechanical ventilation and the cardiovascular system. In: Kreit JW, editor. Mechanical ventilation, 1st ed. New York: Oxford University Press; 2012. pp. 111–126.)
intravascular volume to such patients would not be expected to improve hemodynamics. If, on the other hand, left ventricular preload is inadequate and the
heart is functioning on the ascending portion of the curve, the same decrease in preload will have a much greater hemodynamic effect. Thus, a large
Recommended Reading Fessler HE. Heart-lung interactions: applications in the critically ill. Eur Resp J 1997;10:226–237. Magder S. Clinical usefulness of respiratory variations in arterial pressure. Am J Resp Crit Care Med 2004;169:151–155.
Case Conferences: The Clinical Physiologist
ventilation-related change in systolic blood pressure predicts that volume loading will significantly increase stroke volume and blood pressure. The link between mechanical ventilation–induced systolic blood pressure variation and volume responsiveness exists only during passive mechanical ventilation. This is because inspiratory and expiratory efforts generate pleural pressure swings that may produce systolic blood pressure variation even in patients with optimal left ventricular preload. For the same reason, systolic blood pressure variation during spontaneous breathing is also a poor predictor of volume responsiveness. Although several investigators have attempted to quantify the change in systolic blood pressure that separates volume responders from nonresponders during passive mechanical ventilation, these results are difficult to generalize because of differences in ventilator settings and study populations. n Author disclosures are available with the text of this article at www.atsjournals.org.
Perel A. The physiological basis of arterial pressure variation during positive-pressure ventilation. Reanimation 2005;14:162–171. Feihl F, Broccard AF. Interactions between respiration and systemic hemodynamics. Part 1. Intensive Care Med 2009;35:45–54. Feihl F, Broccard AF. Interactions between respiration and systemic hemodynamics. Part 2. Intensive Care Med 2009;35:198–205.
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