Continued...

Fluid Resuscitation
Intravenous access for fluid resuscitation and inotrope /vasopressor infusion is more difficult to attain in children than in adults. The American Heart Association has well established Pediatric advanced life support (PALS) guidelines for emergency establishment of intravascular support including intraosseous access (14). On the basis of many studies, it is accepted that aggressive fluid resuscitation with crystalloids or colloids is of fundamental importance to survival of septic shock in children (8,15). There is only one randomized, controlled trial comparing the use of colloid with crystalloid resuscitation (dextran, gelatin, lactated Ringers, or saline) in children with dengue shock (8). All these children survived, regardless of the fluid used, but the longest time to recovery from shock occurred in children who received lactated Ringers. Among patients with the narrowest pulse pressure, there was a suggestion that colloids were more effective than crystalloids in restoring normal pulse pressure. Fluid infusion is best initiated with boluses of 20 mL/kg over 5-10 mins, titrated to clinical monitors of cardiac output, including heart rate, urine output, capillary refill, and level of consciousness. A 60 ml syringe filled with fluid drawn via the fluid bag with a three-way connection can be conveniently used to push fluid boluses in the absence of a volumetric pump.

Children normally have a lower blood pressure than adults and can prevent reduction in blood pressure by vasoconstriction and increasing heart rate. Therefore, blood pressure by itself is not a reliable endpoint for assessing the adequacy of resuscitation. However, once hypotension occurs, cardiovascular collapse may soon follow.

Hepatomegaly occurs in children who are fluid overloaded and can be a helpful sign of the adequacy of fluid resuscitation. Other practical ways to assess fluid overload are jugular venous distension, heart size and pulmonary congestion on chest x ray. Gold standard still remains the measurement of a central venous pressure.

Large fluid deficits typically exist, and initial volume resuscitation usually requires 40-60 mL/kg but can be much higher (9,15,16). As a word of caution in neonates use of aggressive fluid therapy may be limited by patency of ductus arteriosus, risk of intraventricular hemorrhage and right heart failure due to pulmonary hypertension.

Vasopressors / Inotropes
(Should Only Be Used After Appropriate Volume Resuscitation) Children with severe sepsis can present with low cardiac output and high systemic vascular resistance (cold shock, more common scenario), high cardiac output and low systemic vascular resistance, or low cardiac output and low systemic vascular resistance shock. Early inotropic support should be started in the case of fluid refractory shock or a life threatening hypotension when fluid bolus has been initiated. Dopamine is the first choice of support for the pediatric patient with hypotension refractory to fluid resuscitation. The choice of vasoactive agent is determined by the clinical examination. Dopamine-refractory shock may reverse with epinephrine (adrenaline) or norepinephrine (noradrenaline) infusion (16). Pediatric patients with low cardiac output states may benefit from use of dobutamine. The use of vasodilators can reverse shock in pediatric patients who remain hemodynamically unstable with a high systemic vascular resistance state, despite fluid resuscitation and implementation of inotropic support (9,16). Nitrovasodilators with a very short half-life (nitroprusside or nitroglycerin) are used as first-line therapy for children with epinephrine-resistant low cardiac output and elevated systemic vascular-resistance shock. Inhaled nitric oxide reduced extracorporeal membrane oxygenation use when given to term neonates with persistent pulmonary artery hypertension of the newborn and sepsis in a randomized, controlled trial (17). When pediatric patients remain in a normotensive low cardiac output and high vascular resistance state, despite epinephrine and nitrovasodilator therapy, then the use of a phosphodiesterase inhibitor should be strongly considered, such as milrinone(12,18,19). Vasopressin therapy should be considered in warm shock unresponsive to fluid and norepinephrine.

Early antibiotics
After appropriate cultures are taken early use of broad spectrum systemic antimicrobial therapy based on clinical suspicion is reasonable although no randomized studies exist in children. Adult data supports use early appropriate antibiotics to impact favourably on morbidity from septic shock