Case Report

Volume 000, Number 000, October 2025, pages 000-000

Angiotensin II to Treat Intraoperative Vasoplegic Shock in an Infant

Shock is a life-threatening condition marked by impaired oxygen delivery, heightened oxygen demand, or the body’s inability to utilize oxygen effectively—ultimately leading to cellular and tissue hypoxia [1]. Clinically, it often presents as hypotension and arises from a wide range of underlying causes, all of which carry high mortality if not promptly recognized and treated. Shock is broadly categorized into four types: distributive, hypovolemic, cardiogenic, and obstructive. A notable subtype, vasoplegic shock, falls under distributive shock and is defined by an abnormally low systemic vascular resistance (SVR) despite normal or even elevated cardiac output. This mismatch results in dangerously low blood pressure and poor tissue perfusion. Vasoplegic shock commonly occurs in early sepsis, after cardiopulmonary bypass, during severe anaphylaxis, or in the aftermath of trauma resuscitation. Uniquely challenging, it often proves refractory to standard fluid resuscitation and conventional adrenergic vasopressors, making it a critical therapeutic dilemma.

We present the use of a novel vasoactive agent, angiotensin II (AT-II), to treat intraoperative vasoplegic shock during bilateral nephrectomy in an infant. Options to treat vasoplegic shock are discussed, previous reports of the use of AT-II in infants and children reviewed, and its role in the treatment of vasoplegic shock presented.

Review of this case and presentation followed the guidelines of the Institutional Review Board of Nationwide Children’s Hospital (Columbus, OH). Written, informed consent was obtained for the use of de-identified information for publication.

The patient was a 5-week-old male infant with stage 5 chronic kidney disease secondary to autosomal recessive polycystic kidney disease (ARPKD), who presented for bilateral nephrectomy and placement of a peritoneal dialysis catheter.

The patient was born at 33 weeks weighing 2,140 g by vaginal delivery to a 20-year-old female. Pregnancy was complicated by late prenatal care starting at 30 weeks. At that time, an ultrasound showed anhydramnios and magnetic resonance imaging revealed bilaterally enlarged kidneys concerning for ARPKD. The patient was admitted to the neonatal intensive care unit (NICU) after birth where ARPKD was confirmed by ultrasound. The patient was also found to have a large right pneumothorax, small pericardial effusion, and pulmonary hypoplasia on chest radiograph. Respiratory insufficiency was initially treated with continuous positive airway pressure (CPAP) followed by endotracheal intubation and surfactant administration. The pneumothorax was treated by needle thoracostomy shortly after birth and aquapheresis was started for management of his volume status. Surgery occurred at the age of 5 weeks, with a patient weight of 3 kg. Immediately prior to surgery, the patient was receiving erythropoietin to stimulate red blood cell production, nicardipine (2 - 3 µg/kg/min) to maintain the mean arterial pressure (MAP) at 45 - 60 mm Hg, fentanyl (1.5 µg/kg/h) to provide sedation during mechanical ventilation, and bivalirudin to provide anticoagulation during aquapheresis. The preoperative physical examination was notable for significantly enlarged, distended, and palpable kidneys bilaterally, along with trace non-pitting peripheral edema. The patient was afebrile with a pulse of 147 beats/min, with a ventilator rate of 40 breaths/min, pressure support 12 cm H₂O, and oxygen saturation of 97% with an inspired oxygen concentration of 35%. The trachea had been previously intubated with a 3.0 mm endotracheal tube (ETT). Cardiovascular exam was significant for a systolic murmur with a regular rate and rhythm with normal peripheral pulses and capillary refill of 2 s. The preoperative complete blood count including hemoglobin, hematocrit, and platelet count was within normal range. Laboratory evaluation revealed sodium 141 mEq/L, potassium 4.1 mEq/L, chloride 103 mEq/L, and glucose of 100 mg/dL. Although the preoperative blood urea nitrogen and creatinine were elevated at 52 and 1.28 mg/dL, respectively, the values were stable over the past week. The prothrombin time was elevated, but stable at 15.5 s with an international normalized ratio (INR) of 1.2; activated partial thromboplastin time (APTT) was elevated at 55 with a normal fibrinogen.

The patient was kept nil per os for 8 h prior to surgery and transported to the operating room, where standard American Society of Anesthesiologists’ monitors were applied. Anesthesia was maintained with sevoflurane (expired concentration 0.5-1.5%), dexmedetomidine (1.5 µg/kg/h), and fentanyl (2 - 3 µg/kg/h). Neuromuscular blockade was provided by intermittent doses of rocuronium. MAP was maintained at 45 - 60 mm Hg with nicardipine (1 - 2 µg/kg/min). Additional intraoperative analgesia was provided by two bolus doses of morphine (0.1 mg/kg/dose). Dextrose 20% in 0.9% sodium chloride was infused at 10 mL/h via a pre-existing central venous catheter. Prophylaxis against surgical site infections included cefazolin (50 mg/kg) every 3 h. Intraoperatively, during the bilateral nephrectomy, the nicardipine infusion was discontinued as the MAP was less than 40 mm Hg. A further decrease in the MAP failed to respond to fluid administration (20 - 30 mL/kg of 5% albumin), and vasopressor support was initiated with epinephrine at 0.02 µg/kg/min when the MAP persisted at 30 mm Hg. No response was noted when the epinephrine was increased to 0.05 µg/kg/min. Approximately 15 min after the start of the epinephrine infusion, presuming that the low MAP was related to vasoplegic shock, an AT-II infusion was started at 5 ng/kg/min and then increased over the next 15 - 20 min to 10 ng/kg/min, resulting in an MAP of 50 - 60 mm Hg. The MAP was sustained throughout the remainder of the procedure at 50 - 60 mm Hg. Postoperatively, AT-II was continued at 5 - 10 ng/kg/min to maintain the MAP at 50 - 70 mm Hg as the epinephrine infusion was weaned and then discontinued. On postoperative day 3, the AT-II infusion was slowly weaned in increments of 1 ng/kg/min over 18 - 24 h and then discontinued. On postoperative day 2, patient was given hydrocortisone to support MAPs.

Postoperatively, the patient was continued on aquapheresis to maintain his volume status and has subsequently been transitioned to peritoneal dialysis and was stable on his ventilator settings. His hemodynamic and respiratory status were stable during the postoperative course. Given the presence of multiple comorbid conditions including chronic respiratory failure and the ongoing need for PD, he remains hospitalized in the NICU to address these issues.

Vasoplegia, marked by a dangerously low SVR, can arise from a range of critical conditions—including sepsis, anaphylaxis, and the inflammatory aftermath of cardiopulmonary bypass. Its pathophysiology is multifaceted, driven by a complex interplay of intrinsic and extrinsic mechanisms that disrupt normal vascular tone. On the intrinsic side, potent vasodilators such as nitric oxide (NO), endothelin-1, and prostanoids are key contributors [2-5]. Meanwhile, extrinsic influences—particularly the vascular system’s diminished responsiveness to endogenous vasoconstrictors like catecholamines, vasopressin, and glucocorticoids—further amplify and prolong the vasoplegic state. This intricate balance between molecular signaling and vascular reactivity makes vasoplegia a particularly challenging condition to manage. The primary goals in the treatment of vasoplegic shock are twofold: identifying and addressing the underlying cause, and providing hemodynamic support to maintain adequate oxygen delivery and tissue perfusion. Management typically involves targeted therapy based on the etiology, along with interventions aimed at restoring MAP. These may include careful fluid resuscitation and the use of vasoactive agents to counteract the profound systemic vasodilation characteristic of the low SVR state.

Successful management of vasoplegic shock requires a balance of maintaining adequate SVR to ensure organ perfusion while mitigating adverse effects associated with high-dose vasopressor therapy [2]. Traditional pharmacological approaches to vasoplegic shock primarily involve α-adrenergic agonists such as phenylephrine or norepinephrine, dopamine, and non-adrenergic vasoactive agents such as vasopressin [3, 4]. These agents may have a narrow therapeutic index, with escalating doses leading to dose-limiting toxicities including myocardial ischemia, arrhythmias, and peripheral vasoconstriction that can compromise organ perfusion. Adjunctive therapies have included the administration of corticosteroids or methylene blue, which inhibits guanylate cyclase, an important enzyme in the nitric oxide signaling pathway [5, 6]. Corticosteroids increase the responsive of the adrenergic receptors of the vasculature, increasing cytosolic calcium availability, and increasing vascular tone. In adult ICU practice, hydrocortisone has been used alone or as part of hydrocortisone, ascorbic acid and thiamine (HAT) therapy that includes hydrocortisone, ascorbic acid, and thiamine. Dopamine has been used as a naturally occurring catecholamine and precursor to norepinephrine to increase systemic arterial pressure and stimulate the myocardium.

Given the limitations and potential toxicities of conventional therapies discussed above, there has been growing interest in alternative agents with novel mechanisms of action—most notably, AT-II, a naturally occurring hormone with potent vasoconstrictive properties and a central role in cardiovascular homeostasis. AT-II is an octapeptide and a key component of the renin-angiotensin-aldosterone system (RAAS), a hormonal system involved in regulating blood pressure, fluid, and electrolyte balance [7]. AT-II exerts potent vasoconstrictor effects primarily through activation of AT-II type 1 receptors located on vascular smooth muscle cells. Binding to these receptors triggers a cascade of intracellular events, including increased cytosolic calcium, leading to smooth muscle contraction and subsequent vasoconstriction. Beyond its direct vasoconstrictive properties, AT-II also promotes aldosterone release, sodium reabsorption, and can modulate activity of the sympathetic nervous system.

Preliminary clinical experience with exogenous AT-II has shown promise in adults with refractory vasoplegic shock. The Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial, an international, randomized, double-blind, placebo-controlled trial of 344 adult patients, demonstrated improved MAP in adults with vasodilatory shock refractory to conventional vasopressor therapy, defined as shock being treated with more than 0.2 µg/kg/min of norepinephrine, or the equivalent dose of another vasopressor [8]. Response to angiotensin was defined as an increase in the MAP to ≥ 75 mm Hg or an increase in MAP from baseline ≥ 10 mm Hg without an increase in the dose of other vasopressor agent. Significantly more patients in the AT-II arm than in the placebo arm achieved the primary end point. Additionally, there was a greater increase in MAP in the AT-II group than placebo. The trial highlighted AT-II as a viable therapeutic option for patients with distributive shock unresponsive to adrenergic agents and vasopressin.

While well-established in adult critical care, the published literature on AT-II use in pediatric patients, particularly infants, has been limited [9-12]. Bailey et al outlined the use of AT-II in two pediatric patients (2 and 8 years of age) who required high-dose vasopressor therapy in the setting of vasoplegic shock [10]. The first patient was in vasodilatory septic shock as a result of pneumonia and was receiving norepinephrine 0.05 µg/kg/min and dopamine 15 µg/kg/min prior to the initiation of AT-II at 1.25 ng/kg/min. Three hours after starting AT-II, all other traditional vasopressor therapy was successfully discontinued. The second patient in this case series was admitted with septic shock in the setting of meningitis and encephalitis. There was no response to multiple vasoactive infusions (epinephrine 0.1 µg/kg/min, norepinephrine 0.2 µg/kg/min, and vasopressin 2 mU/kg/min). AT-II was started at 1.25 ng/kg/min and eventually increased to 39.1 ng/kg/min. Within 90 min of initiation, the norepinephrine and vasopressin infusions were weaned and discontinued. Due to a progressive central nervous system (CNS) insult, the patient developed refractory cerebral edema, increased intracranial pressure (ICP), and expired. Additional anecdotal experience was reported by Razdan et al in their use of AT-II to treat vasodilatory shock on day of life 5 in a preterm infant with bilateral renal agenesis [11]. Vasodilatory shock was unresponsive to the administration of dopamine, vasopressin, epinephrine, and hydrocortisone. AT-II was started at 1.25 ng/kg/min and eventually titrated to up 40 ng/kg/min over 4 days. Within the first day of AT-II therapy, the patient’s blood pressure had stabilized and other vasoactive agents were discontinued.

In the largest cohort to date in infants and children, Tezel et al reported their experience using AT-II in a cohort of 23 children (median age 10.4 years) from a single-center, retrospective case series [12]. The majority of patients presented with vasodilatory shock secondary to sepsis and severe acute kidney injury and required high-dose vasopressor therapy with a median norepinephrine equivalent dose (NED) of 0.65 µg/kg/min. AT-II was started at a median dose of 10 ng/kg/min with a median infusion duration of 27 h. At each assessment point, there was an improvement in the NED and MAP. Although overall survival in the cohort was limited to 30%, the authors observed that survivors received AT-II therapy significantly earlier than non-survivors—by nearly 3 days (91.5 vs. 161 h)—highlighting the potential importance of timely intervention. The authors concluded that AT-II decreased NED and improved MAP in critically ill children with catecholamine-resistant vasodilatory shock (CRVS). They further recommended further prospective work to examine optimal timing of AT-II therapy and patient selection.

In summary, our case contributes to the growing body of anecdotal evidence supporting the potential utility of AT-II in pediatric patients with distributive or vasoplegic shock refractory to conventional adrenergic therapy. While data in this population remain limited, these observations—when considered alongside more robust findings from adult studies—suggest a role for AT-II, particularly in cases involving escalating vasoactive support without adequate improvement in MAP.

Acknowledgments

None to declare.

Financial Disclosure

None to declare.

Conflict of Interest

None to declare.

Informed Consent

Informed consent was obtained for hospital/anesthetic care and the use of de-identified information for publication.

Author Contributions

NS: preparation of initial, subsequent, and final drafts; GAR: direct patient care, and review of drafts and final document; BW: review of drafts and final document; JDT: concept, writing, and review of all drafts.

Data Availability

Any inquiries regarding supporting data availability of this study should be directed to the corresponding author.

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