The Effect of Early Norepinephrine on Stroke Volume Index, Cardiac Index, Lactate, and Arterial Elastance in Pediatric Septic Shock

The complexity of pediatric septic shock arise from its varied pathophysiology, which includes systemic inflammation, cardiovascular collapse, and multiple organ dysfunction. Current standard treatments, which primarily focusedon fluid resuscitation, had exhibited several problems. Excessive fluid resuscitation has been associated with complications such as fluid overload, which may cause conditions such as pulmonary edema and organ dysfunction, leading to worsened outcomes. This emphasizes the need for alternative therapeutic strategies that can effectively manage hemodynamic instability while minimizing the risks of fluid overload. In adult patients, the early use of vasopressors has been recommended to restore perfusion in patients with septic shock, compared to repeated fluid loading. However, previous research on the use of norepinephrine and the preload status of the pediatric population is still limited. In addition, the use of fluid resuscitation does not always exhibit the desirable response, which is the increase of blood pressure. This is because the blood pressure depends not only on the stroke volume but also the vascular resistance. Consequently, predicting blood pressure elevation after fluid resuscitation remains challenging. Based on previous research, arterial elastance has the potential to predict the increase of blood pressure in response to fluid administration. Thus, this study aimed to investigate the effects of early administration of fluid resuscitation combined with norepinephrine in pediatric septic shock patients and evaluate the useof arterial elastance as a predictor of blood pressure response following fluid resuscitation. Finally, this study will also evaluate the parameters such as stroke volume index, cardiac index, lactate clearance , arterial elastance in pediatric patients with septic shock who were resuscitated using the hemodynamic support guidelines according to the Surviving Sepsis Campaign protocols.

The complexity of pediatric septic shock arise from its varied pathophysiology, which includes systemic inflammation, cardiovascular collapse, and multiple organ dysfunction. Current standard treatments, which primarily focused on fluid resuscitation, had exhibited several problems. Excessive fluid resuscitation has been associated with complications such as fluid overload, which may cause conditions such as pulmonary edema and organ dysfunction, leading to worsened outcomes. This emphasizes the need for alternative therapeutic strategies that can effectively manage hemodynamic instability while minimizing the risks of fluid overload. In adult patients, the early use of vasopressors has been recommended to restore perfusion in patients with septic shock, compared to repeated fluid loading. However, previous research on the use of norepinephrine and the preload status of the pediatric population is still limited. In addition, the use of fluid resuscitation does not always exhibit the desirable response, which is the increase of blood pressure. This is because the blood pressure depends not only on the stroke volumebut also the vascular resistance. Consequently, predicting blood pressure elevation after fluid resuscitation remains challenging. Based on previous research, arterial elastance has the potential to predict the increase of blood pressure in response to fluid administration. Thus, this study aimed to investigate the effects of early administration of fluid resuscitation combined with norepinephrine in pediatric septic shock patients and evaluate the use of arterial elastance as a predictor of blood pressure response following fluid resuscitation. Finally, this study will also evaluate the parameters such as stroke volume index, cardiac index, lactate clearance , arterial elastance in pediatric patients with septic shock who were resuscitated using the hemodynamic support guidelines according to the Surviving Sepsis Campaign protocols.

Research Objectives

1. Evaluate the changes in preload between the pediatric septic shock patients receiving fluid loading with early administration of norepinephrine compared to those who only receive fluid loading.
2. Evaluate the changes in stroke volume index, cardiac index, and mean arterial pressure between the pediatric before and after treatment in both groups.
3. Evaluate the changes in lactate clearance before and after treatment in both groups.
4. Assess the sensitivity and specificity of arterial elastance as a predictor of blood pressure response in patients receiving fluid resuscitation.

Eligibility Criteria:
Inclusion Criteria:

1. Patients aged 3 months to 18 years with critical condition
2. Suspected or confirmed infection, indicated by fever accompanied by signs of shock:

   1. Mean arterial pressure 5th percentile, or
   2. Systolic pressure ≤ 5th percentile, or
   3. Diastolic pressure ≤ 5th percentile, or
   4. Wide pulse pressure (diastolic pressure \< half of systolic pressure), or
   5. Tachycardia accompanied by one or more of the following signs: Altered mental status, capillary refill time \> 2 seconds, temperature difference between extremities and core body, weaker peripheral arterial pulsation compared to the central pulsation, bounding pulse, mottled skin.

Exclusion Criteria:

1. Contraindication of fluid loading (signs of fluid overload)
2. Burn injury, massive bleeding, dengue hemorrhagic fever.
3. Cardiogenic shock.
4. Deep anesthesia.