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A 28-week gestation infant, birth weight 1.3 kg, had been managed with non-invasive respiratory support since birth. Patient was placed over-night (day of life (DOL) 2 to DOL 3) from CPAP to NIMV (16/6 x 30) with 21% FiO₂. This was done in the context of occasional apnea and bradycardia events .
On day of life 3, the infant developed increased frequency of apnea and bradycardia, prompting intubation to secure the airway. FiO₂ requirements were modest around 25%, and ventilator settings included a tidal volume of 5 mL/kg, PEEP of 5, and a rate of 40. Prior to the intubation, the radiography demonstrated appropriate chest expansion, with appropriate position of the umbilical venous and umbilical arterial line. There was some decrease bowel gaz pattern with no frank pneumatosis. There was bilateral haziness of the lungs on chest radiography.
An arterial blood gas revealed metabolic acidosis: pH 7.14, pCO₂ 46 mmHg, HCO₃⁻ 15 mmol/L, base deficit -13, and a lactate of 5.9 mmol/L. Laboratory results showed leukopenia (WBC 3.1 x10⁹/L), stable hemoglobin at 125 g/L, and a concerning drop in platelets from 194 to 35 x10⁹/L.
Since birth, the heart rate was 150-160 bpm with a baseline mean blood pressure of 35 mmHg. At the time of assessment on DOL 3, the heart rate was 165-170 and blood pressure had dropped to 34/18 mmHg (mean 22). Two normal saline boluses of 10 mL/kg were administered by the medical team without meaningful improvement.
On examination, the infant appeared lethargic with decreased reactivity. The infant exhibited signs of warm shock, including flash capillary refill and warm extremities. The patient was initiated on meropenem and vancomycin. A targeted neonatal echocardiogram (TNE) was requested to investigate the hemodynamic instability and rising lactate. The TNE revealed high RVO and LVO, normal RV and LV systolic function, a PFO that is left to right and an unrestrictive ductus about the size of the left pulmonary artery with left to right shunt. The descending abdominal aorta exhibited holodiastolic retrograde flow. The TNE was compatible with a state of low SVR, and low PVR/SVR ratio, with the steal effect worsening the context of the vasodilatatory shock picture and leading to low diastolic pressures.
Our center is part of a comparative effectiveness study evaluating dopamine versus norepinephrine in the management of prematurity-related septic shock. As part of the study design, our center committed to follow the dopamine algorithm until study results. Accordingly, the patient received escalating doses of dopamine, starting at 5 mcg/kg/min, then 10, and ultimately 15 mcg/kg/min. Dopamine is known to increase pulmonary vascular resistance (PVR), which was considered potentially beneficial in this case given the presence of a left-to-right ductal shunt. The goal was to reduce transductal flow and favor systemic perfusion. Blood pressure increased with dopamine administration, but this was accompanied by a significant rise in heart rate. Due to worsening metabolic acidosis and rising lactate levels, dopamine was discontinued, and norepinephrine was initiated along with hydrocortisone supplementation.
Although the patient demonstrated some clinical improvement on norepinephrine, a repeat TNE performed later in the afternoon showed findings similar to the initial study. Lactate remained elevated, and there was no urine output. Norepinephrine was subsequently increased to 0.1 mcg/kg/min. Vasopressin was added as adjunct therapy and titrated up to 1.5 milliunits/kg/min, while norepinephrine was escalated to 0.3 mcg/kg/min. Following this, the patient’s condition stabilized: urine output resumed, mean arterial pressure increased to approximately 35 mmHg and above, and lactate levels gradually declined (with improvement in pH). Hemodynamics normalized under the combined vasopressor therapy. Blood cultures later confirmed Escherichia coli bacteremia, supporting the diagnosis of septic shock.
Trends of pH, lactate and bicarbonate. Values at the bottom represent pre-shock measurements; values at the top reflect those obtained after resolution of shock while on vasopressor support.
First TnECHO
First TnECHO
Normal LV shortening fraction, in the face of high SVR. We were expecting a hyperdynamic shortening fraction. This is why we repeated the TNE in the afternoon, to make sure that with increasing afterload the LV was not failing, and would otherwise require inotropic support.
LVOT diameter for LVO estimation.
Normal biventricular function. At this point, the ventricles and atriums appear appropriately filled in terms of preload. Heart rate is 170 bpm.
Normal TAPSE for GA (RV systolic function)
Flow entering RV and LV via atrioventricular valves (no stenosis, no insufficiency).
LVO is high - more than 300 mL/kg/min, which is likely a reflection of the left to right PDA and the from the low SVR state with compensatory increase in LVO.
No LVOT obstruction.
No pericardial effusion, good contractility from mitral valve to apex of the LV"
IVC is distended with forward flow towards the RA. This indicates appropriate filling, but also that the RV end diastolic pressure are not too high. IVC may be of normal caliber or distended because of mechanical ventilation. There is no clear indication of low preload at this point.
Left to right PFO in the subcostal short axis view. The LA pressure is higher than the RA pressure, which is not surprising in the context of the ductal physiology.
The D wave is within normal limit and there is a nice tracing of pulmonary venous flow, indicating that there is adequate pulmonary blood flow. A PPHN picture would be accomopanied with low velocities in the pulmonary veins because of the low filling of pulmonary vascular bed.
Left to right pulsatile unrestrictive PDA with low velocities at peak systole and end-diastole.
Retrograde holodiastolic flow in the descending aorta. This is likely secondary to the ductal steal. Although, to confirm, we would need to do Dopplers in the ascending arch as there could be a component of steal within the cerebral circulation as there is sometimes preferential vasodilation of the cerebral circulation in septic shock by either loss of autoregulation (passive circulation), or compensatory mechanism.
Vasopressors and their properties are encircled here.
Dopamine
Dopamine theoretically exerts β₁-adrenergic effects at intermediate doses (5–10 mcg/kg/min) to increase heart rate and myocardial contractility, and α₁-adrenergic effects at higher doses (>10 mcg/kg/min) to promote vasoconstriction and increase systemic vascular resistance (SVR). These differential effects by dosages have not been convincely proven in the neonatal period. In this case, where the infant presented with warm shock physiology—high cardiac output and low SVR—dopamine was selected with the hope of improving perfusion pressure and mitigating systemic hypotension. Additionally, because dopamine can increase pulmonary vascular resistance (PVR), it was thought to possibly reduce the magnitude of left-to-right ductal shunting by decreasing the transductal pressure gradient. However, the patient exhibited a significant tachycardic response without sustained improvement in metabolic parameters, prompting a change in therapy.
Norepinephrine
Norepinephrine was initiated following the failure of dopamine to reverse the hemodynamic instability and metabolic acidosis. Norepinephrine is a potent α₁-adrenergic agonist with mild β₁ activity, making it well-suited for managing vasoplegic shock by increasing SVR and improving diastolic and mean arterial pressure, with relatively limited (but some) impact on heart rate. In this preterm neonate with features of vasodilatory septic shock and ongoing ductal steal physiology, norepinephrine was expected to restore systemic perfusion by reversing the marked vasodilation and improving end-organ blood flow. The clinical response was favorable, with signs of improved hemodynamics and stabilization of lactate levels, although additional support was required due to persistent low urine output and hypotension.
Vasopressin
Vasopressin was introduced as adjunct therapy in the setting of refractory hypotension despite escalating doses of norepinephrine. Unlike catecholamines, vasopressin acts through non-adrenergic V1 receptors to induce vasoconstriction, particularly in the peripheral and splanchnic circulation. This makes it especially useful in cases of catecholamine-resistant vasodilatory shock. In this patient, vasopressin was used to raise SVR and support diastolic blood pressure, which was particularly important given the presence of retrograde diastolic flow in the descending aorta and ongoing ductal shunting, and to promote coronary perfusion. Vasopressin also helped enhance renal perfusion, which corresponded with the return of urine output and further improvement in systemic perfusion. The combined effect of norepinephrine and vasopressin led to normalization of blood pressure and progressive resolution of metabolic acidosis.
Hydrocortisone
Hydrocortisone was added to address the possibility of relative adrenal insufficiency, a common contributor to refractory shock in preterm neonates, particularly during severe infections like sepsis. Beyond its endocrine support, hydrocortisone enhances the sensitivity of vascular adrenergic receptors to catecholamines, thus augmenting the effectiveness of agents like norepinephrine. In this case, hydrocortisone was used in conjunction with norepinephrine to help restore vascular tone and reduce vasopressor requirements. Its addition likely contributed to the stabilization of the infant’s hemodynamic status and facilitated recovery from shock.
Some important articles on Norepinephrine in the context of neonatal septic shock
Some important articles on Norepinephrine in the context of neonatal septic shock
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