25 2.9.4.6 Diagnostic use of Procalcitonin in bacterial endocarditis
Despite not being the gold standard in diagnosis of endocarditis, elevated procalcitonin levels have been seen in patients with endocarditis. It has been shown to be highly sensitive and specific in diagnosing endocarditis.114 High serum PCT levels has been reported in those with infective endocarditis compared with those with other diagnosis.115
2.9.4.7 Diagnostic use of Procalcitonin in gastroenteritis
Gastroenteritis, a leading cause of death among under five years of age. It can be due to both infectious and non-infectious causes. Many microbial pathogens have been identified.
Procalcitonin was found to be a good diagnostic marker of bacterial gastroenteritis.116 Also in study of diarrhoea with various etiologies, procalcitonin was found to be lower in children with viral gastroenteritis.117
26 2.10.1 Initial resuscitation and infection issues
The primary goals of management in the first few hours following presentation are to maintain oxygenation, ventilation and achieve adequate perfusion. In abnormal or distress respiratory function, oxygen should be administered to the patient via facemask to ensure adequate oxygen saturation. However, in patients that desaturate despite administration of oxygen via facemask, high-flow nasal oxygen or nasopharyngeal continuous positive airway pressure (CPAP) can be used to increase functional residual capacity and reduce the work of breathing.
For fluid resuscitation and inotrope infusion, peripheral intravenous or intraosseeus access should be maintained when a central is not available.
Early intubation and positive pressure mechanical ventilatory support should be considered seriously in young infants and neonates with severe sepsis.
The initial therapeutic outcome of resuscitation include: capillary refill of < 2 seconds, normal pulses with no distinct difference between the peripheral and central pulses, warm extremities, normal blood pressure for age, appropriate urinary output for age (> 1ml/kg/hr), normal mental status and superior vena cava or mixed venous oxygen saturation >70% . In case of a pulmonary artery catheter use especially in children with systemic arterial hypoxaemia such cyanotic congenital heart disease, therapeutic end points of cardiac index
>3.3 and <6.0 L/min/m2 should be aimed for.
27 2.10.2 Antibiotics and source control
Following initial stabilization, prompt initiation of effective antimicrobial therapy against the likely causative agents should be instituted. However, blood cultures should be obtained prior to commencement of antimicrobial therapy. At least two sets of blood cultures must be obtained. These blood cultures should be drawn at the same time if they are obtained from different sites. Cultures of other sites such as urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids should be obtained as dictated by clinical suspicion before antimicrobial therapy. The choice of empiric antibiotic therapy depends on the patient’s history, underlying disease, the clinical syndrome (including involved organs and likely pathogens), and local susceptibility patterns. The chosen antibiotic therapy should include one or more drugs that have activity against the likely pathogens. Antimicrobials can be given intramuscularly or orally until intravenous line access is available.
Inappropriate empiric antimicrobial therapy has been independently associated with increased mortality in septic patients. The antimicrobial regimen should be reassessed after 48 to 72 hours, which includes reviewing the microbiologic and clinical data and de-escalating the therapy if possible.
Appropriate steps should be undertaken to drain infected fluids and abscesses, débride infected soft tissues, and remove infected devices that result in ongoing microbial contamination.
2.10.3 Resuscitation
Fluid resuscitation is one of the essentials of sepsis therapy. Aggressive fluid resuscitation with crystalloids or colloids is of fundamental importance to pediatrics survival of septic
28 shock. Fluid resuscitation should be 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. Hepatomegaly can occur in children who are fluid overloaded and can be a helpful sign of the adequacy of fluid resuscitation. Large fluid deficits typically exist, and initial volume resuscitation usually requires 40–60 mL/kg but can be much higher.
2.10.4 Inotropes/Vasopressors/Vasodilators
Inotropes/vasopressors/vasodilators are commenced after adequate fluid resuscitation.
Children with severe sepsis can present with low cardiac output and high systemic vascular resistance, high cardiac output and low systemic vascular resistance, or low cardiac output and low systemic vascular resistance shock. Depending on which situation exists, inotropic support should be started in the case of fluid refractory shock or a combination of an inotrope together with a vasopressor or a vasodilator. 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 or norepinephrine infusion. 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.
Nitrosovasodilators or prostacyclin or fenoldopam can be used as first-line therapy for children with epinephrine-resistant low cardiac output and high systemic vascular-resistance shock with normal blood pressure.
29 2.10.5 Extracorporeal membrane oxygenation
Extracorporeal membrane oxygenation (ECMO) may be used to support children and neonates with septic shock or sepsis-associated respiratory failure.
2.10.6 Corticosteroids
Hydrocortisone therapy should be reserved for use in children with fluid-refractory, catecholamine resistance shock and suspected or proven (classic) adrenal insufficiency.
Patients at risk include children with severe septic shock and purpura, children who have previously received steroid therapies for chronic illness, and children with pituitary or adrenal abnormalities. There are no strict definitions, but adrenal insufficiency in the case of catecholamine-resistant septic shock is assumed at a random total cortisol concentration
<18µg/dL (496nmol/L). There is no clear consensus for the role of steroids or best dose of steroids in children with septic shock. Dose recommendations vary from 1–2 mg/kg for stress coverage (based on clinical diagnosis of adrenal insufficiency) to 50 mg/kg for empirical therapy of shock followed by the same dose as a 24-hr infusion.
2.10.7 Blood products and plasma therapies
After stabilization and recovery from shock and hypoxaemia, blood transfusion is recommended for hemoglobin value of < 7.0g/dl to target a hemoglobin concentration of 7.0 – 9.0 g/dl. However, erythropoietin should not be used as a specific treatment for anaemia associated with severe sepsis.
Platelets should be administered prophylactically when counts are less than 10,000/mm3 in the absence of apparent bleeding as well as when counts are less than 20,000/mm3 if there is
30 significant risk of bleeding. Higher platelet counts (≥ 50,000/mm3) are advised for active bleeding, surgery or invasive procedures.
Plasma therapies should be used in children to correct sepsis-induced thrombotic purpura disorders, including progressive disseminated intravascular coagulation, secondary thrombotic microangiopathy, and thrombotic thrombocytopenic purpura. Fresh frozen plasma contains high concentration of protein C, antithrombin III and other anticoagulant proteins.
2.10.8 Mechanical ventilation
Lung protective strategies should be provided during mechanical ventilation. Patients with ARDS will require increased PEEP to attain functional residual capacity and maintain oxygenation, and peak pressures above 30 to 35 cm H2O to attain effective tidal volumes of 6 to 8 mL/kg with adequate CO2 removal. In these patients, conventional pressure control ventilation or pressure release ventilation (airway pressure release ventilation) or high-frequency oscillatory ventilation can be used to maintain oxygenation with higher mean airway pressures using an “open” lung ventilation strategy. These modes can require a mean airway pressure 5cm H2Ohigher than that used with conventional ventilation in order to be effective. This can reduce venous return leading to greater need for fluid resuscitation and vasopressor requirements.
2.10.9 Sedation/analgesia/drug toxicities
Appropriate sedation and analgesia should be provided for children who are mechanically ventilated. Propofol should be avoided in children less than 3 years who require long-term sedation because of reported fatal metabolic acidosis. Also, the use of etomidate and/ or
31 dexmedetomidine should be discouraged in septic shock because of interference with the adrenal and sympathetic nervous system.
2.10.10 Glycemic control
In pediatric population, blood glucose of ≤ 180mg/dL should be targeted. In general, infants are at risk for developing hypoglycemia when they depend on intravenous fluids. This means that a glucose intake of 4–6 mg/kg/min or maintenance fluid intake with glucose 10%
in sodium chloride 0.45% is advised. Insulin therapy should only be done with frequent glucose monitoring in view of the risks for hypoglycemia.
2.10.11 Diuretics and renal replacement therapy
Diuretics can be used to reverse fluid overload when shock has resolved and if unsuccessful, then continuous veno-venous hemofiltration or intermittent dialysis to prevent greater than 10% total body weight fluid overload should be used.
2.10.12 Deep venous thrombosis (DVT) prophylaxis
Most DVTs in young children are associated with central venous catheters. Femoral venous catheters are commonly used in children, and central venous catheter-associated DVT occurs in approximately 25% of children with a femoral central venous catheter. Heparin-bonded catheters may decrease the risk of catheter-associated DVT.
2.10.13 Stress ulcer prophylaxis
Studies have shown that the rate of clinically important gastrointestinal bleeding in children occurs at rates similar to adults. As in adults, coagulopathy and mechanical ventilation are risk factors for clinically important gastrointestinal bleeding. Stress ulcer prophylaxis
32 strategy is commonly used in mechanically ventilated children, usually with H2 blockers or proton pump inhibitors.
2.10.14 Nutrition
Enteral nutrition should be used in children who can tolerate it and parenteral feeding in those who cannot. Dextrose 10% (always with sodium-containing solution in children) at maintenance rate provides the glucose delivery requirements for newborns and children.
Patients with sepsis have increased glucose delivery needs which can be met by this regimen. Metabolic chart can be used in specific measurement of caloric requirements.
33 CHAPTER THREE
MATERIALS AND METHODS.