Continued...

Inotropic And Vasoactive Agents
Sepsis induced myocardial depression is well documented.

Before cardiac output and perfusion pressure are restored with drugs, electrolyte abnormalities (such as ionized hypocalcemia) that might impair cardiac performances should be corrected. Metabolic acidosis secondary to tissue hypoxia should be managed by treating the cause. Sodium bicarbonate should be given only for severe acidosis that fails to respond to adequate resuscitation.

If signs of shock persist despite adequate volume replacement and perfusion of vital organs is jeopardized, inotropic drugs may be used to improve cardiac output (9).The effects of particular drug in an individual patient are unpredictable and must be closely monitored. Drugs commonly used in pediatric ICU to increase myocardial contractility include :

Dopamine : It has alpha, beta and dopaminergic (delta) actions that are dose dependant. At low doses (< 3 mcg/kg/min) it primarily causes weak renal and splanchnic vasodilatation and at 3mcg to 10mcg/kg/min it exerts a positive myocardial inotropic effect. At higher doses (> 10 mcg/kg/min), it has strong vasoconstricting alpha effect, in addition to positive inotropic effect. So called 'Renal dose' of dopamine (2-5 mcg/kg/min) for renal vasodilatation has been over emphasized and is of less practical significance in clinical setting. The primary indication for dopamine is the need to increase myocardial contractility after preload restoration. Usual dose is 5-20 mcg/kg/min titrated to desired effect. Dopamine (in doses >5 mcg/kg/min) should preferably, be given via central line to prevent ischemic necrosis of the skin.

Dobutamine : It is selective beta 1 agonist. It causes an increase in cardiac contractility and reduces peripheral resistance. The reduction in afterload and improved myocardial performance lowers ventricular filling pressures. Usual dose is 5mcg to 20mcg/kg/min.it should not be used alone in septic shock due to risk of further drop in blood pressure. Dopamine or adrenaline can be used to prevent hypotension due to vasoconstrictive effect.

Adrenaline (Epinephrine): It is an alpha and beta adrenergic agonist. It is used in situations where dominant hemodynamic feature is peripheral vascular failure as in septic shock. At higher doses, severe vasoconstriction can lead to lactic acidosis and renal and splanchnic ischemia. The usual dose is 0.1 mcg/kg/min to 1 mcg/kg/min. It should be titrated closely and minimum dose should be used for required.

Noradrenaline (Norepinephrine): An alpha and beta agonist (alpha > beta effect). Cardiac contractility is increased but it also causes massive increase in myocardial oxygen consumption and afterload, so cardiac output may not actually increase. Usual dose is 0.05 -1 mcg/kg/min. In severe septic shock with hypotension, despite use of adrenaline secondary to intense vasodilatation, noradrenaline may be useful in increasing peripheral vascular resistance to improve blood pressure.

Vasopressin
In severe warm shock with hypotension resistant to noradrenaline, vasopressin may be tried.

Afterload reduction
Caution should be used in using afterload reduction indiscriminately in septic shock without simultaneous inotropic support. Both nitroprusside and nitroglycerin lower systemic vascular resistance in children and are useful afterload reducing agents. These agents act via generation of nitric oxide. Nitroprusside has potent peripheral arterial vasodilating effects. Nitroglycerin is more potent venodilator and pulmonary vasodilator. Close monitoring and volume augmentation are frequently required when vasodilators are used to decrease pulmonary vascular resistance.

Amrinone and milrinone are newer inotropic agents with properties of afterload reduction and myocardial diastolic relaxation (lusotropic effect)(10=12). Milrinone is commonly used for cardiogenic shock, which is frequently associated with septic shock.

Table 3 ACCM Recommendations for neonatal and pediatric septic shock management (3) :

• 0 min - Recognize mental status, poor perfusion
  
  
• 5 min - Maintain airway, establish access push 20ml/kg up to 60ml/kg fluid. Observe in PICU if positive response
  
  
• 15min - Recognize fluid refractory shock, start central line, dopamine, establish arterial monitoring.
  
  
• If fluid refractory dopamine resistant shock(10mic/kg/min), start epinephrine for cold, norepinephrine for warm shock.
  
  
• If Risk of adrenal insufficiency (38-39) give hydrocortisone.
  
  
• Normal BP, Cold shock SVC O2 sat < 70 add vasodilator, consider volume
  
  
• Low BP, Cold shock, SVC O2 sat < 70 - Titrate volume and Epinephrine
  
  
• Low BP, Warm shock : give Norepinephrine, fluid, consider Vasopressin

Early goal directed therapy helps keep the cost and duration of hospital stay to a minimum.

Following section describes the current consensus on management of sepsis in children based on available evidence (2). These guidelines mainly apply to the pediatric age group. These guidelines may not be applicable to the neonatal age group, though occasional reference has been made to the neonatal situations.

Need for early intubation and ventilation
Due to low functional residual capacity, young infants and neonates with severe sepsis may require early intubation (13). Unfortunately, no objective clinical criteria specific to pediatric septic shock for timing of endotracheal intubation (other than the standard indications, which include shock) exist in literature. Therefore it is reasonable to consider endotracheal intubation when shock is persistent even after a volume resuscitation of >40-60 ml/kg. Children with sepsis requiring aggressive fluid resuscitation frequently have worsening tachypnea and increasing oxygen requirement clinically depicting early acute respiratory distress syndrome (ARDS).These patients will require early intubation and mechanical ventilation. The principles of lung-protective strategies (low tidal volumes and permissive hypercapnia) are applied to children as they are to adults. In premature infants, additional attention is paid to avoiding hyperoxemia to prevent retinopathy.