Hyperdynamic circulation

Hyperdynamic circulation is a hemodynamic condition characterized by increased cardiac output, decreased systemic vascular resistance, and reduced mean arterial pressure.^[1] This state reflects widespread arterial vasodilation, often leading to a high-flow circulatory pattern that compensates for perceived hypovolemia but can strain the cardiovascular system.^[2] The condition arises in diverse clinical scenarios, most notably advanced liver cirrhosis with portal hypertension, where splanchnic vasodilation predominates.^[3] Other key etiologies include sepsis, hyperthyroidism (thyrotoxicosis), severe anemia, arteriovenous fistulas or shunts, and less commonly, Paget's disease or beriberi.^[2] In cirrhosis, portal hypertension triggers bacterial translocation and shear stress, promoting the release of vasodilatory mediators.^[4] Pathophysiologically, hyperdynamic circulation begins with peripheral and splanchnic arterial dilation, mediated by overproduction of factors such as nitric oxide, prostacyclin, carbon monoxide, and endocannabinoids, which lower vascular tone and effective circulating volume.^[3] This underfilling activates baroreceptor reflexes, the renin-angiotensin-aldosterone system, and sympathetic nervous system, resulting in tachycardia, expanded plasma volume, and elevated cardiac output to maintain perfusion.^[4] In sepsis, systemic inflammation amplifies this via cytokines like tumor necrosis factor-α and interleukin-6, exacerbating vasodilation.^[2] Clinically, patients exhibit tachycardia, bounding pulses, warm extremities, and wide pulse pressure, often progressing to high-output heart failure with symptoms like dyspnea, edema, and fatigue if untreated.^[2] Management targets underlying causes, such as antibiotics for sepsis or non-selective beta-blockers in cirrhosis, to mitigate complications including hepatorenal syndrome and variceal hemorrhage.^[3]

Fundamentals

Definition

Hyperdynamic circulation refers to a physiological state characterized by increased cardiac output and decreased systemic vascular resistance, often observed in various chronic conditions. It is typically defined by a cardiac output exceeding 8 L/min or a cardiac index greater than 4.2 L/min/m², alongside a systemic vascular resistance below 800 dyn·s·cm⁻⁵, with normal or elevated stroke volume and frequent tachycardia (heart rate >100 bpm).^[5] This circulatory pattern arises as a compensatory response to maintain adequate tissue perfusion despite underlying vasodilation, distinguishing it from normodynamic states where these parameters remain within standard ranges.^[2] The foundational equation for cardiac output, which underpins this hyperdynamic profile, is $CO = HR \times SV$CO=HR×SV, where $CO$CO represents cardiac output, $HR$HR is heart rate, and $SV$SV is stroke volume; in hyperdynamic circulation, elevations in both $HR$HR and $SV$SV contribute to the increased $CO$CO.^[5] The term was first coined in the context of liver cirrhosis studies during the 1950s, notably through the landmark work of Kowalski and Abelmann in 1953, who used cardiac catheterization to demonstrate these hemodynamic alterations in patients with alcoholic cirrhosis.^[6] Unlike high-output heart failure, where the elevated cardiac output fails to meet metabolic demands due to progressive cardiac dysfunction, hyperdynamic circulation often serves as an adaptive, non-pathological mechanism in early stages, preserving organ perfusion without immediate decompensation.^[2] This differentiation highlights hyperdynamic circulation's role as a reversible state driven by systemic factors rather than intrinsic myocardial impairment.^[5]

Key Hemodynamic Features

Hyperdynamic circulation is marked by distinct hemodynamic alterations that reflect an augmented cardiac performance coupled with reduced vascular tone. Central to this state is an elevated cardiac index, typically exceeding 4 L/min/m², surpassing the normal range of 2.5–4.0 L/min/m².^[2] Cardiac output is similarly increased, often greater than 8 L/min at rest, compared to the standard range of 4–8 L/min.^[2] Systemic vascular resistance (SVR) is profoundly decreased, usually below 800 dynes·s·cm⁻⁵, in opposition to the normal values of 800–1200 dynes·s·cm⁻⁵.^[2] This reduction in SVR leads to a widened pulse pressure, calculated as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP): $$\text{PP} = \text{SBP} - \text{DBP}$$PP=SBP−DBP In hyperdynamic circulation, pulse pressure frequently exceeds 60 mmHg, well above the normal 40–60 mmHg, due to the enhanced stroke volume and diminished diastolic pressure.^[7][2] These parameters contribute to observable clinical features, including bounding pulses and warm extremities, indicative of robust peripheral perfusion.^[2] In certain scenarios like sepsis, this hyperdynamic profile is termed "warm shock," characterized by these same circulatory signs without progression to vasoconstriction.^[8]

Pathophysiology

Mechanisms of Vasodilation

Hyperdynamic circulation is characterized by widespread arterial vasodilation, which primarily initiates in the splanchnic circulation and subsequently extends to peripheral vascular beds, resulting in reduced systemic vascular resistance.^[4] This process underlies the low effective arterial blood volume that drives the hemodynamic alterations.^[9] Splanchnic vasodilation represents the initial event, occurring in the mesenteric and splenic arterial beds, which increases portal venous inflow and contributes to the hyperdynamic state.^[3] This localized reduction in vascular tone is mediated by multiple vasodilatory pathways, leading to persistent relaxation of vascular smooth muscle.^[10] The overproduction of nitric oxide (NO) is a central mechanism, primarily through upregulation of endothelial nitric oxide synthase (eNOS) in endothelial cells.^[9] NO diffuses into vascular smooth muscle, activating soluble guanylate cyclase to increase cyclic guanosine monophosphate (cGMP) levels, which promotes dephosphorylation of myosin light chains and vasodilation.^[3] Additional gaseous mediators, such as carbon monoxide (CO) produced via heme oxygenase-1 (HO-1), and prostacyclin (PGI2) derived from cyclooxygenase-1 (COX-1), further enhance this effect by stimulating similar second messenger pathways, including cGMP and cyclic adenosine monophosphate (cAMP).^[4] Humoral factors also play a key role in sustaining vasodilation. Glucagon and substance P, elevated due to impaired hepatic clearance, directly relax vascular smooth muscle and amplify NO release from endothelium.^[9] Endocannabinoids, particularly anandamide, contribute by overactivating cannabinoid-1 (CB1) receptors on endothelial cells, which in turn boost NO production and reduce vasoconstrictor responsiveness.^[3] Endothelial dysfunction exacerbates these processes, characterized by an imbalance favoring vasodilator production over vasoconstrictors, often linked to altered endothelial cell signaling.^[10] Increased shear stress from elevated blood flow further perpetuates vasodilation by mechanically activating eNOS through phosphorylation via Akt kinase and association with heat shock protein 90 (Hsp90).^[4] The peripheral arterial vasodilation theory posits that the initial splanchnic vasodilation triggers a cascade, extending to systemic arteries via similar mediator pathways, thereby amplifying the overall reduction in vascular tone.^[9] This progression from regional to generalized vasodilation is supported by observations of hyporesponsiveness to vasoconstrictors in extrahepatic vessels.^[3]

Compensatory Cardiac and Systemic Responses

In hyperdynamic circulation, the body initiates a series of compensatory mechanisms to counteract the effective hypovolemia resulting from widespread vasodilation, primarily through neurohormonal and cardiac adaptations that aim to preserve systemic perfusion and blood pressure. These responses involve the activation of endogenous vasoconstrictor and volume-retaining systems, which increase cardiac output and expand plasma volume, though they may eventually contribute to further circulatory strain if the underlying vasodilation persists.^[4] The sympathetic nervous system (SNS) plays a central role in these adaptations by responding to reduced mean arterial pressure, leading to increased heart rate (tachycardia) and enhanced myocardial contractility to boost cardiac output. This activation occurs via baroreceptor sensing of arterial underfilling, stimulating norepinephrine release that augments stroke volume and overall hemodynamic performance, particularly in conditions like cirrhosis where baseline cardiac output is already elevated.^[4][1] Parallel to SNS activation, the renin-angiotensin-aldosterone system (RAAS) is stimulated by renal hypoperfusion and low effective circulating volume, promoting sodium retention in the distal tubules and collecting ducts to expand extracellular fluid volume. This results in hypervolemia, which increases preload and supports higher cardiac output by enhancing venous return, though chronic RAAS overactivity can lead to maladaptive fluid overload.^[4][11] Baroreceptors in the carotid sinus, aortic arch, and renal juxtaglomerular apparatus detect the decline in effective arterial blood volume, triggering integrated responses that include non-osmotic release of antidiuretic hormone (ADH, or vasopressin) from the posterior pituitary. ADH acts on V2 receptors in the renal collecting ducts to insert aquaporin-2 channels, facilitating water reabsorption and further contributing to plasma volume expansion, thereby aiding in the maintenance of circulatory stability despite ongoing vasodilation.^[4][12] At the cardiac level, these systemic changes induce remodeling, notably left ventricular dilation, which accommodates the increased preload and stroke volume required for the hyperdynamic state without immediate decompensation. This adaptation involves eccentric hypertrophy to handle higher filling pressures, preserving ejection fraction under resting conditions, though it may predispose to diastolic dysfunction over time.^[4][1]

Etiology

Liver Cirrhosis

In liver cirrhosis, hyperdynamic circulation emerges as a hallmark of advanced disease, primarily driven by portal hypertension resulting from intrahepatic vascular distortion and fibrosis. This condition leads to increased portal pressure, which triggers splanchnic arterial vasodilation and initiates a cascade of systemic hemodynamic changes, including elevated cardiac output and reduced systemic vascular resistance.^[13] The hyperdynamic state is particularly prominent in decompensated cirrhosis, where it contributes to clinical deterioration and complications like renal dysfunction.^[14] The pathogenesis begins with portal hypertension inducing shear stress on splanchnic endothelial cells, which upregulates vasodilator production such as nitric oxide, promoting arterial dilation in the mesenteric bed.^[13] Concurrently, bacterial translocation from the gut, facilitated by intestinal barrier dysfunction and portal hypertensive enteropathy, stimulates endothelial nitric oxide synthase and inflammatory cytokines, further amplifying splanchnic vasodilation and the hyperdynamic response.^[15] This localized vasodilation increases portal inflow, perpetuating the cycle of hypertension and extending vasodilation to peripheral arteries through overflow of vasodilatory factors.^[3] Hyperdynamic circulation is commonly observed in patients with advanced cirrhosis, with studies reporting its presence in up to 20-30% using strict hemodynamic criteria, though it becomes more evident and severe with decompensation.^[5] It worsens progressively as liver function declines, correlating with higher Child-Pugh scores and the onset of complications.^[16] A unique aspect in cirrhosis is the formation of ascites, exacerbated by portal-systemic shunting that diverts blood flow away from the liver, intensifying splanchnic pooling and effective arterial hypovolemia.^[17] Hypoalbuminemia, stemming from impaired hepatic synthesis, lowers plasma oncotic pressure, promoting fluid extravasation into the peritoneal cavity and compounding the underfilling sensed by baroreceptors.^[17] This contrasts with general vasodilation mechanisms by emphasizing the interplay of portal dynamics and protein deficiency in driving fluid retention and third-space losses. The link between hyperdynamic circulation and cirrhosis was first established in the 1950s through studies by Kowalski and Abelmann, who demonstrated increased cardiac output and decreased systemic vascular resistance in patients with alcoholic cirrhosis using early catheterization techniques.^[18] Their observations in decompensated cases laid the foundation for recognizing this syndrome as a core feature of chronic liver disease.

Sepsis and Infections

In sepsis, hyperdynamic circulation represents a hallmark of the early distributive shock phase, driven by systemic inflammation triggered by bacterial endotoxins and pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1).^[19] These mediators induce endothelial dysfunction, leading to excessive nitric oxide (NO) production by inducible NO synthase in vascular smooth muscle and endothelial cells, which causes profound vasodilation and reduced systemic vascular resistance.^[20] Concurrently, cytokines promote capillary leak through disruption of endothelial junctions and adhesion molecules, resulting in extravascular fluid shifts, relative hypovolemia, and maldistribution of blood flow despite adequate or elevated cardiac output.^[19] This inflammatory cascade is central to the pathophysiology of sepsis-induced vasodilation, distinguishing it from other forms of shock.^[21] The hemodynamic profile in sepsis typically evolves through distinct phases. The initial "warm" hyperdynamic phase is characterized by high cardiac output, tachycardia, and warm extremities due to compensatory mechanisms maintaining perfusion amid vasodilation; this stage predominates in the early hours to days of untreated or partially treated sepsis.^[22] If the underlying infection persists or worsens, progression to a late "cold" hypodynamic phase can occur, marked by myocardial depression, declining cardiac output, and vasoconstriction as compensatory reserves fail, often signaling multi-organ dysfunction.^[8] The Surviving Sepsis Campaign guidelines recognize this hyperdynamic state as a key feature of distributive shock in sepsis, emphasizing early fluid resuscitation and vasopressor support to restore perfusion and prevent transition to refractory shock. Hyperdynamic circulation is observed in the majority of patients with early septic shock, with a prevalence of approximately 18%, though precise prevalence varies by diagnostic criteria and timing of assessment.^[23][24] Persistence of the hyperdynamic state, particularly when associated with left ventricular systolic hyperdynamism, correlates with increased short-term mortality, with risks up to 2.5 times higher compared to normodynamic profiles, reflecting ongoing inflammation and organ stress.^[25] This underscores the prognostic importance of monitoring hemodynamic transitions in septic patients to guide timely intervention.^[23]

Other Conditions

Hyperdynamic circulation can occur in physiological states such as pregnancy, where cardiac output increases by 30-50% to support the low-resistance placental circulation and meet elevated maternal and fetal demands.^[26] Similarly, chronic anemia induces a hyperdynamic state through hypoxia-driven peripheral vasodilation, which reduces systemic vascular resistance and elevates cardiac output to enhance oxygen delivery to tissues.^[27] In pathological conditions, thyrotoxicosis results from excess thyroid hormones that accelerate metabolism, decrease peripheral vascular resistance, and thereby increase cardiac output, often leading to a sustained hyperdynamic circulation.^[28] Arteriovenous fistulas create a low-resistance shunt that diverts blood flow, imposing a chronic volume load on the heart and producing high-output cardiac states with elevated cardiac index and wide pulse pressure.^[29] Wet beriberi, stemming from thiamine deficiency, manifests as a hyperdynamic syndrome with vasodilation, increased venous return, and high-output heart failure due to impaired energy metabolism in vascular smooth muscle.^[30] Rarer associations include Paget's disease of bone, where extensive bone hypervascularity increases overall blood flow and can precipitate a high-output circulatory state, particularly in cases of widespread skeletal involvement.^[31] In obesity, chronic volume overload from expanded plasma volume and heightened metabolic needs drives a hyperdynamic circulation, with elevated cardiac output compensating for the increased tissue mass.^[32] Unlike the persistent hemodynamic derangements in cirrhosis or sepsis, hyperdynamic circulation in these conditions typically resolves upon correction of the underlying physiological or pathological trigger, such as delivery in pregnancy, iron supplementation in anemia, or antithyroid therapy in thyrotoxicosis.^[28]

Diagnosis

Clinical Presentation

Hyperdynamic circulation manifests through a variety of observable signs and symptoms that reflect the underlying increase in cardiac output and systemic vasodilation. Patients commonly experience fatigue, which arises from the sustained high-output state taxing the cardiovascular system, as well as dyspnea on exertion due to increased oxygen demands and potential pulmonary congestion.^[2] Orthostatic intolerance is also frequent, stemming from relative hypovolemia despite expanded plasma volume, leading to symptoms like lightheadedness upon standing.^[33] Key physical signs include bounding pulses, detectable as forceful and expansive arterial pulsations in peripheral vessels, and wide pulse pressure exceeding 60 mmHg, resulting from the disparity between elevated systolic and relatively low diastolic pressures.^[34] Flushed skin and warm extremities are prominent, indicative of enhanced peripheral blood flow, often accompanied by hyperthermia in acute settings such as sepsis.^[2] Tachypnea may occur as a compensatory response to metabolic demands or mild hypoxemia.^[35] On physical examination, capillary refill time is typically brisk, less than 2 seconds, reflecting robust peripheral perfusion without evidence of peripheral cyanosis.^[36] In cases with volume expansion, jugular venous distension may be evident, signaling elevated central venous pressure. In chronic conditions like cirrhosis, presentations can be more subtle, with indirect signs such as spider angiomata appearing as small, pulsatile vascular lesions on the skin, linked to the hyperdynamic state and estrogen excess.^[37] These features collectively aid in early bedside recognition of the syndrome.^[38]

Hemodynamic Measurement Techniques

Non-invasive techniques are often the first-line approach for assessing hyperdynamic circulation, particularly in stable patients where clinical signs such as tachycardia and wide pulse pressure suggest the need for objective confirmation.^[39] Echocardiography serves as a cornerstone non-invasive method for estimating cardiac output (CO), utilizing either the Simpson's biplane method to calculate left ventricular end-diastolic and end-systolic volumes or Doppler interrogation of the left ventricular outflow tract to measure stroke volume via velocity-time integral multiplied by the outflow tract area.^[40][41] These approaches allow derivation of CO and subsequent calculation of systemic vascular resistance (SVR), aiding in the identification of hyperdynamic states without procedural risks. Additionally, bioimpedance cardiography provides continuous, non-invasive monitoring of hemodynamic parameters by detecting thoracic electrical impedance changes related to blood flow, which has been validated for delineating hyperdynamic circulation in conditions like cirrhosis.^[42][43] Invasive methods, such as pulmonary artery catheterization (Swan-Ganz catheter), offer the gold standard for precise hemodynamic quantification in critically ill patients. This technique measures CO directly via thermodilution, where a saline bolus is injected into the right atrium and its temperature change is detected in the pulmonary artery, and calculates SVR using the formula SVR = [(mean arterial pressure - central venous pressure) / CO] × 80 dynes·s·cm⁻⁵.^[44] It also enables sampling of mixed venous oxygen saturation (SvO₂), providing comprehensive data on oxygen delivery and extraction.^[45] Diagnosis of hyperdynamic circulation typically requires meeting specific thresholds: CO exceeding 8 L/min or cardiac index exceeding 4 L/min/m², SVR below 900 dynes·s·cm⁻⁵, and SvO₂ greater than 75%, reflecting increased flow, vasodilation, and reduced oxygen extraction, respectively.^[46][5][47] These criteria, derived from pulmonary artery catheterization data, help distinguish hyperdynamic states from other shock phenotypes. Despite their utility, these techniques have limitations. Echocardiography CO estimates carry a variability of 10-20% due to operator dependence, angle of insonation errors, and assumptions in volume calculations.^[48] Pulmonary artery catheterization, while accurate, incurs risks including arrhythmias (up to 17%), infection, thromboembolism, and rare pulmonary artery rupture (0.2-0.5%).^[49][50] Bioimpedance methods may be less reliable in patients with arrhythmias or obesity, potentially underestimating CO in hyperdynamic scenarios.^[43]

Clinical Implications

Associated Complications

Sustained hyperdynamic circulation imposes significant strain on the cardiovascular system, potentially leading to high-output heart failure due to chronic volume overload. This condition arises from persistently elevated cardiac output against reduced systemic vascular resistance, which can overwhelm myocardial compensatory mechanisms over time. In experimental models of portal hypertension, this chronic overload has been associated with eccentric hypertrophy of the left ventricle, characterized by chamber dilation and preserved systolic function initially, but progressing to contractile dysfunction.^[51] Renal complications manifest as functional renal failure, where inadequate effective perfusion occurs despite high cardiac output, resulting from intense renal vasoconstriction triggered by neurohumoral activation. In contexts such as cirrhosis, this can culminate in hepatorenal syndrome, a form of prerenal azotemia with preserved tubular function but markedly reduced glomerular filtration rate. The underlying splanchnic vasodilation exacerbates renal hypoperfusion, highlighting the paradoxical nature of hyperdynamic states in compromising end-organ blood flow.^[3] Pulmonary involvement includes an elevated risk of acute respiratory distress syndrome (ARDS), driven by increased capillary permeability and endothelial dysfunction in the setting of systemic inflammation. Hyperdynamic circulation in advanced liver failure has been observed to contribute to non-infectious ARDS through mechanisms like protein-rich pulmonary edema and alveolar damage, independent of primary pulmonary insults. This complication often resolves with correction of the underlying hemodynamic derangements, underscoring its secondary nature.^[52] Systemically, uncompensated hyperdynamic circulation can progress to multi-organ dysfunction syndrome (MODS), as ongoing vasodilation and volume shifts impair tissue oxygenation across multiple beds. Persistent hyperdynamic states are linked to worse clinical outcomes, including heightened mortality risk compared to normodynamic profiles in critical illnesses like sepsis. For instance, hyperdynamic left ventricular ejection fraction in intensive care settings has been associated with approximately a 1.4-fold increase in 28-day mortality (OR 1.38, 95% CI 1.039–1.842).^[53]

Prognosis and Outcomes

In sepsis-associated hyperdynamic circulation, 30-day mortality rates typically range from 20% to 40%, reflecting the severity of the underlying condition and its impact on cardiac function.^[24][54] A meta-analysis of septic patients confirmed that hyperdynamic left ventricular systolic function is linked to higher short-term mortality, with an odds ratio of 2.37 (95% CI: 1.47–3.80).^[55] In contrast, physiological hyperdynamic states, such as during pregnancy, are associated with more favorable outcomes, with cardiovascular complication rates generally 1–4% and full reversal expected postpartum in uncomplicated cases.^[56] Key predictors of prognosis include the persistence of the hyperdynamic state after initial treatment, which elevates mortality risk by approximately 2.5-fold compared to normalization of cardiac function.^[24] Low stroke volume variation serves as a positive prognostic indicator, suggesting adequate preload and reduced fluid responsiveness needs, which correlates with improved hemodynamic stability.^[16] Long-term outcomes vary by etiology; reversal is achievable in reversible causes like pregnancy, where the hyperdynamic profile typically resolves within weeks postpartum without lasting effects.^[56] However, in chronic conditions such as liver cirrhosis, the hyperdynamic state often persists, contributing to decompensation and a 5-year survival rate below 50%, particularly in advanced disease stages.^[57] Data from the 2023 Surviving Sepsis Campaign updates highlight that early reversal of hyperdynamic features through timely interventions, such as antimicrobial therapy and hemodynamic optimization, significantly improves survival rates and reduces hospital length of stay.^[58]

Management

Treatment of Underlying Cause

The treatment of hyperdynamic circulation primarily involves addressing the underlying etiology to reverse the abnormal hemodynamic state characterized by increased cardiac output (CO) and decreased systemic vascular resistance (SVR).^[5] In patients with liver cirrhosis, non-selective beta-blockers such as propranolol are the cornerstone therapy for portal hypertension, which drives the hyperdynamic circulation; these agents reduce portal pressure by decreasing cardiac output through beta-1 blockade and mitigating splanchnic vasodilation via beta-2 blockade.^[59] Propranolol is typically initiated at 20-40 mg twice daily and titrated to achieve a heart rate of 55-60 beats per minute, thereby normalizing CO and SVR over time.^[60] For refractory cases with complications like variceal bleeding or ascites, transjugular intrahepatic portosystemic shunt (TIPS) placement is indicated to decompress the portal system, leading to hemodynamic stabilization.^[61] In sepsis, the primary interventions target infection control and hemodynamic restoration to counteract the vasodilatory shock underlying hyperdynamic circulation. Broad-spectrum antibiotics should be administered within the first hour of recognition, guided by likely pathogens and local resistance patterns, to eradicate the source of inflammation.^[62] Concurrent source control measures, such as surgical drainage or debridement, are essential to eliminate the infectious focus.^[63] Vasopressors, particularly norepinephrine as the first-line agent, are used to restore SVR when fluid resuscitation alone is insufficient, with early initiation improving shock control.^[64] Norepinephrine dosing typically starts at 0.01-0.05 mcg/kg/min and is titrated to maintain mean arterial pressure above 65 mmHg.^[65] For other conditions, therapy focuses on correcting the specific pathophysiological driver. In hyperthyroidism, antithyroid drugs like methimazole or propylthiouracil inhibit thyroid hormone synthesis, thereby reducing thyroxine levels and alleviating the hyperdynamic state induced by excess thyroid hormone.^[66] Surgical closure or ligation of arteriovenous fistulas is recommended in cases causing high-output failure, as it directly eliminates the low-resistance shunt and normalizes circulation.^[67] In anemia-related hyperdynamic circulation, treatment includes red blood cell transfusion for severe cases (e.g., hemoglobin <7-8 g/dL with heart failure symptoms) to acutely correct the deficit, alongside iron supplementation (oral or intravenous) if iron deficiency is the cause, leading to improved hemoglobin levels and hemodynamic normalization.^[68][69] In Paget's disease, bisphosphonates such as zoledronic acid are used to suppress excessive bone turnover, reducing the associated increased blood flow and hyperdynamic circulation.^[70] For beriberi due to thiamine deficiency, prompt intravenous thiamine administration (100-500 mg daily) is essential to restore normal hemodynamics.^[71] The overarching goal of etiology-specific treatment is to normalize CO and SVR, particularly within 24-48 hours in acute settings like sepsis, to prevent progression to organ dysfunction.^[72]

Supportive and Symptomatic Care

Supportive and symptomatic care in hyperdynamic circulation focuses on stabilizing hemodynamics, optimizing perfusion, and addressing associated physiological stresses without targeting the underlying etiology. Fluid management is a cornerstone, utilizing balanced crystalloids such as lactated Ringer's solution to restore and maintain preload while minimizing risks like hyperchloremic acidosis. Guidelines recommend an initial bolus of at least 30 mL/kg of intravenous crystalloids within the first 3 hours for patients with sepsis-induced hypoperfusion, a common context for hyperdynamic states, followed by ongoing administration guided by dynamic indices of fluid responsiveness.^[73][74] These indices, including pulse pressure variation (PPV), assess respiratory-induced changes in arterial pressure to predict whether additional fluids will augment cardiac output, with PPV greater than 13% indicating potential responsiveness in mechanically ventilated patients.^[75] This approach helps avoid fluid overload, which can exacerbate pulmonary edema in high-output states.^[76] In cases of refractory hypotension due to low systemic vascular resistance (SVR), vasopressors are initiated to restore mean arterial pressure (MAP) while preserving the hyperdynamic cardiac output. Norepinephrine is the first-line agent, administered as a continuous intravenous infusion starting at 0.01–0.05 mcg/kg/min and titrated upward to 0.5 mcg/kg/min or until MAP reaches 65 mmHg.^[73][77] This catecholamine primarily acts on alpha-1 adrenergic receptors to increase SVR with minimal direct inotropic effects at standard doses, thereby supporting perfusion without excessively elevating already high cardiac output.^[78] If norepinephrine requirements exceed 0.25–0.5 mcg/kg/min, adjunctive vasopressin may be added at a fixed low dose of 0.03 units/min to enhance vascular tone synergistically.^[73] Close hemodynamic monitoring is essential to detect and manage complications such as arrhythmias, which can arise from the tachycardia and electrolyte shifts inherent in hyperdynamic circulation. Continuous telemetry with electrocardiographic monitoring is recommended in intensive care settings to identify ventricular or supraventricular arrhythmias promptly, allowing for interventions like electrolyte correction or antiarrhythmic therapy.^[79] Invasive arterial monitoring provides real-time blood pressure data to guide vasopressor titration, while serial lactate measurements track tissue perfusion improvements.^[73] Inotropes such as dobutamine should be avoided unless evidence of myocardial dysfunction is present, as excessive use can further elevate cardiac output and precipitate tachycardia or ischemia in otherwise compensated hyperdynamic states.^[65][22] Nutritional support addresses the hypermetabolic state often accompanying hyperdynamic circulation, particularly in sepsis, where increased energy demands from inflammation and catabolism can lead to rapid muscle wasting. Early enteral nutrition is preferred, initiated within 48–72 hours if gastrointestinal function permits, targeting 25–30 kcal/kg/day of non-protein calories to meet estimated needs without overfeeding, which risks hepatic steatosis or hyperglycemia.^[73][80] Protein provision of 1.2–2.0 g/kg/day supports anabolism, with adjustments based on renal function to prevent azotemia; indirect calorimetry can refine these targets if available, but weight-based estimates suffice in most cases.^[80] This regimen promotes recovery while mitigating complications like renal impairment from undernutrition.^[81]