Vasopressin, An Effective Physiologic “End-Around” to Anesthesia induced Hypotension in Fontan Patients
James DiNardo MD, Viviane Nasr MD, Lindsey Loveland Baptist MD, Susan Nicolson MD
Original Article
Adamson GT, Yu J, Ramamoorthy C, Peng LF, Taylor A, Lennig M, Schmidt AR, Feinstein JA, Navaratnam M. Acute Hemodynamics in the Fontan Circulation: Open-Label Study of Vasopressin. Pediatr Crit Care Med. 2023 Nov 1;24(11):952-960. doi: 10.1097/PCC.0000000000003326. Epub 2023 Jul 18. PMID: 37462430.
Editorial
Ahmed M, Bronicki RA. The Fontan Circulation Holds Water: The Impact of Arginine Vasopressin on the Fontan Circulation. Pediatr Crit Care Med. 2023 Nov 1;24(11):972-975. doi: 10.1097/PCC.0000000000003365. Epub 2023 Nov 2. PMID: 37916881.
This was a prospective, open-label, nonrandomized study designed to describe the acute hemodynamic effect of vasopressin on the Fontan circulation, including systemic and pulmonary pressures and resistances, left atrial pressure, and cardiac index in patients who were referred to the cardiac catheterization laboratory for hemodynamic assessment and/or intervention.1 There were 28 patients studied. Median age was 13.5 (9.1, 17) years, and 16 (57%) patients had a single or dominant right ventricle. The study was accompanied by an insightful editorial.2
Premedication, when required for anxiolysis, was with oral (0.5–0.7 mg/kg, max of 20 mg) or IV (0.5–2 mg) midazolam. General anesthesia was induced with sevoflurane or IV ketamine (0.5–2 mg/ kg). Maintenance of general anesthesia or sedation was with propofol infusion at (25–200 μg/kg/min) plus ketamine infusion (0.5–2 mg/kg/hr). Spontaneous ventilation was maintained with a facemask, nasal cannula, or a SGA. Mean airway pressure was limited to less than or equal to 10 cm H2O for patients supported with an SGA. Patients were maintained on room air or at their pre-catheterization FiO2 if on supplemental oxygen at baseline. A 0.03 U/kg IV (maximum dose 1 unit) bolus of vasopressin was administered over 5 minutes, followed by a maintenance infusion of 0.3 mU/ kg/min (maximum dose 0.03 U/min).
Following vasopressin administration, systolic blood pressure and systemic vascular resistance (SVR) increased by 17.5 (13.0, 22.8) mm Hg and 3.8 (1.8, 7.5) Wood Units, respectively. The pulmonary vascular resistance (PVR) decreased by 0.4 ± 0.4 WU, and the common atrial pressure increased by 1.0 (0.0, 2.0) mm Hg. Neither the pulmonary artery pressure (median difference 0.0 [−1.0, 1.0]) nor cardiac index (0.1 ± 0.3) changed significantly. The authors concluded that in Fontan patients vasopressin may be an option for treating systemic hypotension during sedation or general anesthesia.
As way of review: Preload delivery to the systemic ventricle in the Fontan circulation is non-pulsatile and pressure gradient driven across the pulmonary vascular bed. The mean systemic venous pressure (Pms) (Fontan baffle pressure) drives blood across the resistances created by the cavopulmonary anastomosis and the PVR to be delivered to the common atrium of the systemic ventricle. For a given common atrial pressure the only practical ways to increase preload to the systemic ventricle are to increase Pms or to reduce PVR.3
Venous capacitance is the volume of blood in the venous system at a given pressure and is the sum of stressed and unstressed volume. The capacitance of the venous system is 20 to 30 times greater than that of the arterial system, with 70% of the total blood volume contained in the venous system. Stressed volume is the volume of blood in the venous system that generates a pressure greater than the pressure in the surrounding tissue. The remainder of volume is defined as unstressed volume. Normally, approximately 30% of total blood volume is stressed volume. Thus, for a given venous volume, a decrease in venous capacitance caused by an increase in venous vascular tone will convert a large volume of blood from unstressed to stressed volume, thereby increasing venous pressure. Intravascular volume infusion increases venous pressure for a given venous capacitance because stressed volume increases because of an increase in venous volume. Alternatively, high Pms can be maintained with a low venous volume when venous capacitance is low because stressed volume is larger relative to unstressed volume.3 The sequestration of blood into the venous system can be addressed in 2 ways: by expanding blood volume or by administering a pharmacologic agent capable of reducing venous capacitance.
At baseline compared to normal subjects, patients with Fontan physiology have diminished venous capacitance and thus a smaller unstressed volume. Clinically, the need for sustained high Pms renders these patients vulnerable to acute decreases in intravascular volume and to acute increases in venous capacitance, such as those caused by the direct vasodilation or diminished central sympathetic output accompanying the use of sedative/anesthetic/neuromuscular blockade (NMB) agents. It is noteworthy that neuromuscular blockade (NMB) was not utilized in the management of patients in this study. This is important because the loss of lower extremity muscle tone induced by NMB contributes substantially to conversion of stressed venous volume to unstressed venous volume.
The authors of the editorial2 utilized ventricular pressure-volume loops with superimposed elastance parameters generated by the Harvi cardiovascular simulator (PVLoops, LLC, New York, NY) to simulate the findings of the study.1 The simulations input the data from the study and demonstrated that in order for the results of the simulation to match the reported study results the increase in SVR and the decrease in PVR seen in the study patients must be accompanied by a very modest 5% increase in stressed blood volume. The simulation would predict that this would result in an increase of 1 mm Hg in Pms. Unfortunately, Pms was not reported in this study although it was undoubtedly measured.
Perhaps more importantly, the simulation reveals that SV and thus CO were unchanged because an afterload-induced decrease in SV was offset by a decrease in PVR and an increase in pulmonary blood flow and systemic ventricle EDV. The increase in EDV would be the result of an increase in Pms or a decrease in PVR. It appears that the salutatory effect of vasopressin is due primarily to the increase in SVR and the decrease in PVR given the modest increase in Pms. This is consistent with the fact that all available evidence suggests that vasopressin has, at best, minimal effect on venous capacitance.4 The simulation also reveals that the relatively modest dose of vasopressin used in the study would result in a decrease in EF from 54 to 49% due to uncoupling of the systemic ventricle from the systemic arterial circulation as reflected in an increase in Ea/Ees. In patients with depressed contractility (reduced Ees) a large increase in afterload (Ea) would be expected to catastrophically reduce SV and CO.
So, what is the take home message here? Administration of vasopressin is a reasonable method to maintain SV and increase BP in Fontan patients undergoing sedation/GA with propofol and ketamine in association with spontaneous ventilation. However, use of vasopressin to increase blood pressure in Fontan patients with impaired ventricular function or significantly reduced Pms due to large increases in venous capacitance has no rational physiologic basis.
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References
1. Adamson GT, Yu J, Ramamoorthy C, Peng LF, Taylor A, Lennig M, Schmidt AR, Feinstein JA, Navaratnam M: Acute Hemodynamics in the Fontan Circulation: Open-Label Study of Vasopressin. Pediatr Crit Care Med 2023; 24: 952-960
2. Ahmed M, Bronicki RA: The Fontan Circulation Holds Water: The Impact of Arginine Vasopressin on the Fontan Circulation. Pediatr Crit Care Med 2023; 24: 972-975
3. Jolley M, Colan SD, Rhodes J, DiNardo J: Fontan physiology revisited. Anesth Analg 2015; 121: 172-182
4. Feldheiser A, Gelman S, Chew M, Stopfkuchen-Evans M: Vasopressor effects on venous return in septic patients: a review. Eur J Anaesthesiol 2021; 38: 659-663