Heart Failure With Preserved Ejection Fraction: A Comprehensive Review and Update of Diagnosis, Pathophysiology, Treatment, and Perioperative Implications.

Almost three-quarters of all heart failure patients who are older than 65 have heart failure with preserved ejection fraction (HFpEF). The proportion and hospitalization rate of patients with HFpEF are increasing steadily relative to patients in whom heart failure occurs as result of reduced ejection fraction. The predominance of the HFpEF phenotype most likely is explained by the prevalence of medical conditions associated with an aging population. A multitude of age-related, medical, and lifestyle risk factors for HFpEF have been identified as potential causes for the sustained low-grade proinflammatory state that accelerates disease progression. Profound left ventricular (LV) systolic and diastolic stiffening, elevated LV filling pressures, reduced arterial compliance, left atrial hypertension, pulmonary venous congestion, and microvascular dysfunction characterize HFpEF, but pulmonary arterial hypertension, right ventricular dilation and dysfunction, and atrial fibrillation also frequently occur. These cardiovascular features make patients with HFpEF exquisitely sensitive to the development of hypotension in response to acute declines in LV preload or afterload that may occur during or after surgery. With the exception of symptom mitigation, lifestyle modifications, and rigorous control of comorbid conditions, few long-term treatment options exist for these unfortunate individuals. Patients with HFpEF present for surgery on a regular basis, and anesthesiologists need to be familiar with this heterogeneous and complex clinical syndrome to provide successful care. In this article, the authors review the diagnosis, pathophysiology, and treatment of HFpEF and also discuss its perioperative implications.

The Physiology of Oxygen Transport by the Cardiovascular System: Evolution of Knowledge.

The heart, vascular system, and red blood cells play fundamental roles in O2 transport. The fascinating research history that led to the current understanding of the physiology of O2 transport began in ancient Egypt in 3000 BC, when it was postulated that the heart was a pump serving a system of distributing vessels. Over 4 millennia elapsed before William Harvey (1578-1657) made the revolutionary discovery of blood circulation, but it was not until the 20th century that a lucid and integrative picture of O2 transport finally emerged. This review describes major research achievements contributing to this evolution of knowledge. These achievements include the discovery of the systemic and pulmonary circulations, hemoglobin within red blood cells and its ability to bind O2, and diffusion of O2 from the capillary as the final step in its delivery to tissue. The authors also describe the classic studies that provided the initial description of the basic regulatory mechanisms governing heart function (Frank-Starling law) and the flow of blood through blood vessels (Poiseuille's law). The importance of technical advances, such as the pulmonary artery catheter, the blood gas analyzer and oximeter, and the radioactive microsphere technique to measure the regional blood flow in facilitating O2 transport-related research, is recognized. The authors describe how religious and cultural constraints, as well as superstition-based medical traditions, at times impeded experimentation and the acquisition of knowledge related to O2 transport.

Right Ventricular Perfusion: Physiology and Clinical Implications.

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.

Cricoid Pressure Controversies: Narrative Review.

Since cricoid pressure was introduced into clinical practice, controversial issues have arisen, including necessity, effectiveness in preventing aspiration, quantifying the cricoid force, and its reliability in certain clinical entities and in the presence of gastric tubes. Cricoid pressure-associated complications have also been alleged, such as airway obstruction leading to interference with manual ventilation, laryngeal visualization, tracheal intubation, placement of supraglottic devices, and relaxation of the lower esophageal sphincter. This review synthesizes available information to identify, address, and attempt to resolve the controversies related to cricoid pressure. The effective use of cricoid pressure requires that the applied force is sufficient to occlude the esophageal entrance while avoiding airway-related complications. Most of these complications are caused by excessive or inadequate force or by misapplication of cricoid pressure. Because a simple-to-use and reliable cricoid pressure device is not commercially available, regular training of personnel, using technology-enhanced cricoid pressure simulation, is required. The current status of cricoid pressure and objectives for future cricoid pressure-related research are also discussed.

Preoxygenation: Physiologic Basis, Benefits, and Potential Risks.

Preoxygenation before anesthetic induction and tracheal intubation is a widely accepted maneuver, designed to increase the body oxygen stores and thereby delay the onset of arterial hemoglobin desaturation during apnea. Because difficulties with ventilation and intubation are unpredictable, the need for preoxygenation is desirable in all patients. During emergence from anesthesia, residual effects of anesthetics and inadequate reversal of neuromuscular blockade can lead to hypoventilation, hypoxemia, and loss of airway patency. In accordance, routine preoxygenation before the tracheal extubation has also been recommended. The objective of this article is to discuss the physiologic basis, clinical benefits, and potential concerns about the use of preoxygenation. The effectiveness of preoxygenation is assessed by its efficacy and efficiency. Indices of efficacy include increases in the fraction of alveolar oxygen, increases in arterial oxygen tension, and decreases in the fraction of alveolar nitrogen. End points of maximal preoxygenation (efficacy) are an end-tidal oxygen concentration of 90% or an end-tidal nitrogen concentration of 5%. Efficiency of preoxygenation is reflected in the rate of decline in oxyhemoglobin desaturation during apnea. All investigations have demonstrated that maximal preoxygenation markedly delays arterial hemoglobin desaturation during apnea. This advantage may be blunted in high-risk patients. Various maneuvers have been introduced to extend the effect of preoxygenation. These include elevation of the head, apneic diffusion oxygenation, continuous positive airway pressure (CPAP) and/or positive end-expiratory pressure (PEEP), bilevel positive airway pressure, and transnasal humidified rapid insufflation ventilatory exchange. The benefit of apneic diffusion oxygenation is dependent on achieving maximal preoxygenation, maintaining airway patency, and the existence of a high functional residual capacity to body weight ratio. Potential risks of preoxygenation include delayed detection of esophageal intubation, absorption atelectasis, production of reactive oxygen species, and undesirable hemodynamic effects. Because the duration of preoxygenation is short, the hemodynamic effects and the accumulation of reactive oxygen species are insufficient to negate its benefits. Absorption atelectasis is a consequence of preoxygenation. Two approaches have been proposed to reduce the absorption atelectasis during preoxygenation: a modest decrease in the fraction of inspired oxygen to 0.8, and the use of recruitment maneuvers, such as CPAP, PEEP, and/or a vital capacity maneuver (all of which are commonly performed during the administration of anesthesia). Although a slight decrease in the fraction of inspired oxygen reduces atelectasis, it does so at the expense of a reduction in the protection afforded during apnea.

Carbon Dioxide and the Heart: Physiology and Clinical Implications.

Carbon dioxide (CO2) is an end product of aerobic cellular respiration. In healthy persons, PaCO2 is maintained by physiologic mechanisms within a narrow range (35-45 mm Hg). Both hypercapnia and hypocapnia are encountered in myriad clinical situations. In recent years, the number of hypercapnic patients has increased by the use of smaller tidal volumes to limit lung stretch and injury during mechanical ventilation, so-called permissive hypercapnia. A knowledge and appreciation of the effects of CO2 in the heart are necessary for optimal clinical management in the perioperative and critical care settings. This article reviews, from a historical perspective: (1) the effects of CO2 on coronary blood flow and the mechanisms underlying these effects; (2) the role of endogenously produced CO2 in metabolic control of coronary blood flow and the matching of myocardial oxygen supply to demand; and (3) the direct and reflexogenic actions of CO2 on myocardial contractile function. Clinically relevant issues are addressed, including the role of increased myocardial tissue PCO2 (PmCO2) in the decline in myocardial contractility during coronary hypoperfusion and the increased vulnerability to CO2-induced cardiac depression in patients receiving a ß-adrenergic receptor antagonist or with otherwise compromised inotropic reserve. The potential use of real-time measurements of PmO2 to monitor the adequacy of myocardial perfusion in the perioperative period is discussed.

Regional tolerance to acute normovolemic hemodilution: evidence that the kidney may be at greatest risk.

OBJECTIVE: To evaluate the regional tolerance to acute normovolemic hemodilution (ANH). DESIGN: Prospective animal study. SETTING: University research laboratory. PARTICIPANTS: Nine anesthetized (isoflurane) dogs. INTERVENTIONS: Hematocrit reduced in 10% decrements using dextran-for-blood exchange until cardiac insufficiency observed. MEASUREMENTS AND MAIN RESULTS: Cardiac index (CI) was measured using thermodilution and regional blood flow (RBF) in myocardium, brain, spinal cord, kidney, liver, duodenum, pancreas, spleen, skeletal muscle, and skin with radioactive microspheres. Oxygen delivery (DO2) was calculated from the product of respective blood flow and arterial oxygen content. Systemic oxygen extraction (EO2) and oxygen consumption (VO2) were calculated. Increases in CI during ANH were inadequate to prevent decreases in systemic DO2; however, an increased systemic EO2 maintained VO2 during graded ANH to hematocrit<10%. In the myocardium, brain, and spinal cord, increases in RBF were sufficient to maintain DO2 across the entire range of hematocrits, but this was not the case in the other organs studied. Of note, renal DO2 first decreased at a hematocrit of 30% and was only 25% of baseline at a hematocrit of 10%. CONCLUSIONS: During graded ANH, increases in RBF were sufficient to maintain DO2 in only the heart, brain, and spinal cord. The especially marked decrease in DO2 in the kidney, combined with previous physiologic studies demonstrating its inability to augment EO2, suggest that this organ may be the most at risk of hypoxic damage during ANH.

MYOCARDIAL OXYGENATION DURING ACUTE NORMOVOLEMIC HEMODILUTION: IMPACT OF HYPOCAPNIC ALKALOSIS.

BACKGROUND: Increases in myocardial blood flow preserve myocardial oxygenation during moderate acute normovolemic hemodilution. Hypocapnic alkalosis (HA) is known to cause coronary vasoconstriction and increase hemoglobin-oxygen affinity. We evaluated whether these effects would compromise myocardial oxygenation during hemodilution. METHODS: Eighteen anesthetized dogs were studied. Myocardial blood flow (MBF) was measured with radioactive microspheres. Arterial and coronary sinus samples were analyzed for oxygen content and plasma lactate. Myocardial oxygen supply, oxygen uptake, and lactate uptake were calculated. HA (PaCO2, 23 ± 2 (SD); pHa, 7.56 ± 0.03) was induced by removal of dead space tubing at baseline (n = 8) and during hemodilution (n = 10), with hematocrit at 43 ± 4% and 19 ± 2%, respectively. RESULTS: Hemodilution during normocapnia caused decreases in arterial oxygen content (19.9 ± 2.4 to 9.3 ± 1.2 ml/100; P < 0.05) and the coronary arteriovenous 02 difference (13.0 ± 3.0 to 6.4 ± 0.9 ml/100ml; P < 0.05). MBF increased (52 ± 12 to 111 ± 36 ml/min/100g; P < 0.05) to maintain myocardial oxygen supply and oxygen uptake. Myocardial lactate uptake increased (31 ± 19 to 68 ± 35 µeq/min/100g; P < 0.05). At normal hematocrit, HA decreased MBF (57 ± 18 to 45 ± 10 ml/min/100; P < 0.05), implying vasoconstriction, accompanied by decreased myocardial oxygen supply. These myocardial effects of HA were not apparent during hemodilution. HA did not alter myocardial lactate uptake during hemodilution. CONCLUSION: When HA was induced during hemodilution, its ability to cause coronary vasoconstriction was lost, and myocardial oxygenation remained well preserved.

The mechanism of increased blood flow in the brain and spinal cord during hemodilution.

BACKGROUND: Hemodilution is accompanied by an increase in cerebral blood flow, but whether this is due to vasodilation in response to reduced arterial oxygen content, reduced blood viscosity, or a combination of these mechanisms is a matter of debate. We performed the current study to gain insight into this question by evaluating the effect of hemodilution on (1) vasodilator reserve and (2) the level of blood flow during hypercapnia-induced vasodilation in regions of the brain and spinal cord. METHODS: Sixteen mongrel dogs were anesthetized with halothane 0.9% (1 minimum alveolar concentration) while their lungs were mechanically ventilated. Radioactive microspheres (15 µm) were used to measure regional blood flow (RBF) in the cerebral cortex, cerebellum, pons, medulla, and spinal cord (cervical, thoracic, and lumbar segments). Arterial blood pressure was measured via an aortic catheter. Vasodilator reserve was assessed from the ratio of RBF during hypercapnia (PaCO2 approximately 65 mm Hg) to RBF before hypercapnia. PaCO2 was increased by the addition of dead-space tubing without changing the ventilator settings. The dilating effects of hypercapnia within the central nervous system (CNS) were assessed with hematocrit normal (group 1; n = 8) and after induction of isovolemic hemodilution to a hematocrit of 19 ± 4 (SD) with 5% dextran (group 2; n = 8). RESULTS: Hemodilution increased RBF (P < 0.0001) and decreased the vasodilator reserve ratio (P < 0.05) in all regions of the brain and spinal cord; the ratios during hemodilution (group 2) were only 48% to 68% of those without hemodilution (group 1). The level of RBF during hypercapnia was not significantly different in the absence and presence of hemodilution (cerebral cortex: mean, 122 mL/min/100 g vs mean, 108 mL/min/100 g; 95% confidence interval of the difference (95% CID), -53 to 26; P = 0.46; cerebellum: mean, 117 mL/min/100 g vs mean, 100 mL/min/100 g; 95% CID, -52 to 18; P = 0.32; pons: mean, 83 mL/min/100 g vs mean, 73 mL/min/100 g; 95% CID, -12 to 31; P = 0.35; medulla: mean, 96 mL/min/100 g vs mean, 82 mL/min/100 g; 95% CID, -11 to 40; P = 0.25; cervical spinal cord: mean, 61 mL/min/100 g vs mean, 52 mL/min/100 g; 95% CID, -18 to 34; P = 0.51; thoracic spinal cord: mean, 35 mL/min/100 g vs mean, 46 mL/min/100 g; 95% CID, -30 to 8; P = 0.24; lumbar spinal cord: mean, 54 mL/min/100 g vs mean, 58 mL/min/100 g; 95% CID, -25 to 15; P = 0.61). Neither hypercapnia alone nor combined with hemodilution affected mean arterial blood pressure (P = 0.78 and P = 0.81, respectively). CONCLUSIONS: Hemodilution caused recruitment of the vasodilator reserve, suggesting that vasodilation played a role in the increase in RBF throughout the CNS. Although the mean values for RBF during hypercapnia were similar with and without hemodilution, a large variation in the responses precluded a conclusive determination of whether or not reduced blood viscosity also contributed to the hemodilution-induced increases in RBF. A dependence on vasodilation would limit autoregulatory capability throughout the CNS during hemodilution, which would enhance the risk for ischemia if hypotension was superimposed.

The effectiveness of cricoid pressure for occluding the esophageal entrance in anesthetized and paralyzed patients: an experimental and observational glidescope study.

BACKGROUND: In the last 2 decades, the effectiveness of cricoid pressure (CP) in occluding the esophageal entrance has been questioned. Recent magnetic resonance imaging studies yielded conflicting conclusions. We used real-time visual and mechanical means to assess the patency of the esophageal entrance with and without CP in anesthetized and paralyzed adult patients. METHODS: One hundred seven, nonobese ASA physical status I and II patients were recruited for the study. A cricoid force of 30 N was used. This force was standardized by using a weighing scale before application of CP in each patient. After oxygen administration, anesthetic induction, neuromuscular blockade, and establishment of manual ventilation with FIO2 = 1.0, the view of the glottis and esophageal entrance was visualized, and video recordings were obtained by using a Glidescope video laryngoscope. Attempts to insert 2 gastric tubes (GTs), size 12 and 20 F, into the esophagus were made by a "blinded" operator without and with CP, the timing of which was randomized. A successful insertion of a GT in the presence of CP was considered evidence of a patent esophageal entrance (ineffective CP), whereas an unsuccessful insertion of a GT was considered evidence of an occluded esophageal entrance (effective CP). After the attempts to insert the GTs were completed, tracheal intubation was performed while CP was applied. The position of the esophageal entrance in relation to the glottis (midline versus lateral) was assessed from the video recordings, with and without CP. RESULTS: We stopped the study when 79 patients (41 men and 38 women) qualified for and completed the study (2-sided Clopper-Pearson confidence interval (CI) 95% to 100%, n = 72). Advancement of either size GT into the esophagus could not be accomplished during CP in any patient but was easily done in all subjects when CP was not applied. This occurred whether the esophageal entrance was in a midline position or in a left or right lateral position relative to the glottis. Esophageal patency was visually observed in the absence of CP, whereas occlusion of the esophageal entrance was observed during CP in all patients. Without CP, the esophageal entrance was in a left lateral position in relation to the glottis in 57% ([95 % CI, 45%-68%)] of patients, at midline in 32% (CI, 22%-43%), and in a right lateral position in 11% (CI, 5%-21%). The position did not change with CP. CONCLUSIONS: The current study provides additional visual and mechanical evidence supporting a success rate of at least 95% by using a cricoid force of 30 N to occlude the esophageal entrance in anesthetized and paralyzed normal adult patients. The efficacy of the maneuver was independent of the position of the esophageal entrance relative to the glottis, whether midline or lateral.

Gastric tubes and airway management in patients at risk of aspiration: history, current concepts, and proposal of an algorithm.

Rapid sequence induction and intubation (RSII) and awake tracheal intubation are commonly used anesthetic techniques in patients at risk of pulmonary aspiration of gastric or esophageal contents. Some of these patients may have a gastric tube (GT) placed preoperatively. Currently, there are no guidelines regarding which patient should have a GT placed before anesthetic induction. Furthermore, clinicians are not in agreement as to whether to keep a GT in situ, or to partially or completely withdraw it before anesthetic induction. In this review we provide a historical perspective of the use of GTs during anesthetic induction in patients at risk of pulmonary aspiration. Before the introduction of cricoid pressure (CP) in 1961, various techniques were used including RSII combined with a head-up tilt. Sellick initially recommended the withdrawal of the GT before anesthetic induction. He hypothesized that a GT increases the risk of regurgitation and interferes with the compression of the upper esophagus during CP. He later modified his view and emphasized the safety of CP in the presence of a GT. Despite subsequent studies supporting the effectiveness of CP in occluding the esophagus around a GT, Sellick's early view has been perpetuated by investigators who recommend partial or complete withdrawal of the GT. On the basis of available information, we have formulated an algorithm for airway management in patients at risk of aspiration of gastric or esophageal contents. The approach in an individual patient depends on: the procedure; type and severity of the underlying pathology; state of consciousness; likelihood of difficult airway; whether or not the GT is in place; contraindications to the use of RSII or CP. The algorithm calls for the preanesthetic use of a large-bore GT to remove undigested food particles and awake intubation in patients with achalasia, and emptying the pouch by external pressure and avoidance of a GT in patients with Zenker diverticulum. It also stipulates that in patients with gastric distension without predictable airway difficulties, a clinical and imaging assessment will determine the need for a GT and in severe cases an attempt to insert a GT should be made. In the latter cases, the success of placement will indicate whether to use RSII or awake intubation. The GT should not be withdrawn and should be connected to suction during induction. Airway management and the use of GTs in the surgical correction of certain gastrointestinal anomalies in infants and children are discussed.