1

CASE REPORT SEPSIS Presenters : Shalini Shanmugalingam M. Aripandi Wira Day/Date Supervisor : : dr. Wisman Dalimunthe, Sp.A(K)

CHAPTER 1 INTRODUCTION

1.1. Background Tuberculosis is an ancient disease that is known to have existed in prehistoric times, it remains one of the most important infectious disease in the world.
1

Tuberculosis was recognized to be an infectious disease until

1882 when Koch identified Mycobacterium tuberculosis. 2

Tuberculosis still is one of the deadliest disease in the world killing nearly 2 million people every year. 1 More than nine per cent of all tuberculosis cases occur in the developing countries, where limited resources are available for optimal treatment.3 Tuberculosis continues to be an important cause of morbidity and mortality for worldwide.4

According to statistics, one third of the world populations are infected with Tuberculosis.4 In 2011, nearly 9 million people around the world become sick with TB disease.5 From the total 9 million new cases of tuberculosis , 1 million are pediatrics age < 15 years old.5 A total of 10,528 TB cases (a rate of 3.4 cases per 100,000 persons) were reported in the United States in 2011. Both the number of TB cases reported and the case rate decreased; this represents a 5.8% and 6.4% decline, respectively, compared to 2010.5

Annually, 250.000

new cases of tuberculosis in

6

Indonesia and

approximately 100.000 death because of tuberculosis. Tuberculosis is the main cause of the death among the infection disease and the 3rd cause of death at all ages after cardiovascular and acute respiratory infection.6 Di negara berkembang,TB pada anak berusia <15 tahun adalah 15% dari seluruh kasus TB, sedangkan di negara maju, lebih rendah yaitu 5%-7%. Pada survei nasional di Inggris dan Wales yang berlangsung selama setahun pada tahun 1983, didapatkan bahwa 452 anak berusia <15 tahun menderita TB.14 Laporan mengenai TB anak di Indonesia jarang didapatkan, diperkirakan jumlah kasus TB anak adalah 5%-6% dari total kasus TB. Berdasarkan laporan tahun 1985, dari 1261 kasus TB anak berusia <15 tahun, 63% di antaranya berusia <5 tahun. Hasil penelitian di dua kecamatan di Kotamadya Bandung tahun 19992001, didapatkan 4,3% (63/1482) anak usia 659 bulan, menderita TB.15 Data seluruh kasus TB anak dari tujuh rumah sakit Pusat Pendidikan Indonesia selama 5 tahun (1998-2002) dijumpai 1086 kasus TB dengan angka kematian bervariasi dari 0%-14,1%. Kelompok usia terbanyak 12-60 bulan (42,9%), sedangkan bayi <12 bulan didapatkan 16,5%.16 Laporan hasil Riset Kesehatan Dasar (Riskesdas) tahun 2007, didapatkan prevalensi 12 bulan TB paru klinis di Indonesia 1% dengan kisaran 0,3% (Lampung) sampai 2,5% (Papua). Berdasarkan kelompok umur dijumpai prevalensi TB, kurang dari 1 tahun 0,47%, 14 tahun 0,76% dan antara 514 tahun 0,53%. 16 Selama tahun 1985-1992, peningkatan TB paling banyak terjadi pada usia 25-44 tahun (54,5%), diikuti oleh usia 0-4 tahun (36,1%), dan 5-12 tahun (38,1%). Pada tahun 2005, diperkirakan kasus TB naik 58% dari tahun 1990, 90% di antaranya terjadi di negara berkembang. Di

Amerika Serikat dan Kanada, peningkatan TB pada anak berusia 0-4 tahun 19%, sedangkan pada usia 5-15 tahun 40%. Di Asia Tenggara selama 10 tahun, diperkirakan jumlah kasus baru 35,1 juta, 8% di antaranya (2,8 juta) disertai infeksi HIV. M

1.2. Objective The aim of this study is to explore more about the theoretical aspects on sepsis, and to integrate the theory and apply it to the case that we found in clinical settings. CHAPTER 2 LITERATURE REVIEW

2.1. Definition The systemic inflammatory response syndrome (SIRS) in pediatrics requires the presence of abnormal temperature (hypothermia and hyperthermia) or leukocytosis, in the presence of one other criterion (abnormal temperature, leukocytosis, tachypnea, or tachycardia).4 Sepsis is defined as systemic inflammatory response syndrome (SIRS) associated with infection triggered by a known or highly suspected pathogen. Severe sepsis is defined as sepsis in the setting of acute respiratory distress syndrome, cardiovascular organ dysfunction, or two or more other organ dysfunctions (respiratory, renal, hematologic, neurologic, or hepatic).4,5 Septic shock is defined clinically as the presence of tachycardia and poor perfusion with or without hypotension, the latter being marker of decompensated shock and not required to make the diagnosis of septic shock as in adults.6

2.2. Epidemiology

In the developing world, sepsis accounts for 60-80% of lost lives per year in childhood, killing more than 6 million neonates and children yearly and is responsible for > 100.000 cases of maternal sepsis. Every hour, about 36 people die from sepsis.2 Age is a major inuence on the epidemiology of severe sepsis in the United States. Differences are prevalent among children of different ages and between children and adults. Most strikingly, adults and children differ in physiology, predisposing diseases, and sepsis management strategies. For example, premature birth is an obvious risk factor for pediatric sepsis that is not relevant in adults. Similarly, national vaccination programs may have larger effects on sepsis in pediatric vs. adult patients. Severe sepsis among infants is dominated by perinatal events.7 After infancy, epidemiologic borders between populations are less distinct; however, age-related differences continue to occur, especially regarding underlying diseases, which occur in nearly half (49%) of children who develop severe sepsis.7 Worldwide, 1.6 million neonates die every year from infection8 and 60% of deaths in developing countries occur as a result of communicable disease. Fortunately, sophisticated diagnostic tests and treatment strategies are not requisite to improving sepsis outcomes.7 According to the site of infection and microbiologic etiology, the majority of infections causing sepsis were respiratory (64%), followed by digestive and urinary tract infections (18% and 12% respectively). Respiratory infections predominated in toddlers (45% of the cases), whereas digestive sepsis was particularly common in infants (36%). From the microbiologic aspect, gramnegative bacteria caused the majority of infections that evolved with sepsis. Enterobacteriaceae caused most of gram-negative infections (59%), with Escherichia coli (56%) and Klebsiella pneumoniae (12%) being the most frequent pathogens. Pseudomonas aeruginosa (10%) was the third most frequent agent of Gram-negative sepsis. The most common Gram-positive infecting organism was

Staphylococcus aureus (75%). Atypical pathogens were identified in a minority of patients (4%).9

2.3. Etiology and risk factor Sepsis may develop as a complication of a localized infection or may follow colonization and mucosal invasion by virulent pathogens (see Table 2-1). Children 3 month to 3 year of age are at risk for occult bacteremia that will occasionally progress to sepsis. Patients at risk for sepsis include infants, children with serious injuries, children on chronic antibacterial therapy, malnourished children, and children with chronic medical problems. Also, children who are immune suppressed (transplant recipients on immunosuppressive regimens, patients on chemotherapeutic agents or corticosteroids, patients with acquired or congenital immune deficiencies) are at an increased risk for complications from infection, including sepsis and septic shock.10 The infectious agents associated with sepsis in pediatric patients vary with the patient's age and immune status. In the neonatal age group, group B streptococcus, Escherichia coli, Listeria monocytogenes, enteroviruses, and herpes simplex virus are the pathogens most commonly associated with sepsis. In older children Streptococcus pneumoniae, Neisseria meningitidis, and Staphylococcus aureus (methicillin-sensitive or resistant) are more common. Toxic shock syndrome from group A streptococcus or S. azrreus can also be seen in older children. Rickettsia rickettsi causing Rocky Mountain spotted fever occurs in endemic areas and can lead to septic shock. Nosocomial (hospitalacquired) infections pose a special risk to immunocompromised patients. Intravenous and arterial catheters, urinary catheters, and endotracheal tubes are portals for the development nosocomial infections. Invasive procedures can also lead to nosocomial infections. Infections with gram-negative bacteria (e.g., Escherichia coli, Pseudomonas, Acinetobacter, Klebsiella, Enterobacter, Serratia) and fungi (e.g., Candida, Aspergilus) most often occur in immunocompromised and hospitalized patients colonized with these organisms. Polymicrobial sepsis occurs in high-risk patients and is associated with catheters, gastrointestinal disease,

neutropenia, and malignancy. Unusual pathogens should be suspected in patients who have traveled or been exposed to products or people from distant lands or who are immunocompromised secondary to malignancy, T- or B-cell defects, or asplenia (acquired or congenital). Pseudobacteremia may be associated with contaminated heparin flush solutions, intravenous solutions, albumin,

cryoprecipitate, and infusion equipment. Contaminants include water-borne organisms such as Burkholderia cepacia, Pseudomonas aeruginosa, and Serratia.10

Table 2-1 Differential diagnosis of SIRS10 INFECTION Bacteremia or meningitis Viral illness Encephalitis Rickettsiae Syphilis Vaccine reaction Toxin-mediated reaction GASTROINTESTINAL Gastroenteritis with dehydration Volvulus Intussusception Appendicitis Peritonitis (spontaneous, associated with perforation or peritoneal dialysis) Hepatitis Hemorrhage CARDIOPULMONARY Pneumonia Pulmonary emboli Congestive heart failure Arrhythmia Pericarditis Myocarditis METABOLICENDOCRINE Adrenal insufficiency Electrolyte disturbances Diabetes insipidus Diabetes mellitus Inborn errors of metabolism Hypoglycemia Reye's syndrome NEUROLOGIC and others Intoxication Intracranial hemorrhage Infant botulism Trauma Guillain-Barr syndrome Myasthenia gravis Anaphylaxis Hemolytic-uremic syndrome Kawasaki disease Erythema multiforme Hemorrhagic shock encephalopathy syndrome

HEMATOLOGIC Anemia Methemoglobinemia Splenic sequestration crisis Leukemia or lymphoma

Sepsis is more often occur in children with risk factor. The risk factor for sepsis can be seen in the table below.11 Table 2-2 Risk Factor for Sepsis11 1. Prematurity 2. Age 3. Immune deficiency Malnutrition A-gamma-globulinemia Sickle cell anemia Severe combined immunodeficiency

AIDS Asplenism Complement Deficiency Neutrophl chemotactic factor defect

4. History of Current illness Malignancy Galactosemia Paraplegia Extensive burn injury 5. Iatrogenic Urinary catheterization Surgery 2.4. Pathogenesis10

Nephrotic syndrome Urinary tract infection gonococcus Intravenous drug addiction Endotracheal intubation Continuous peritoneal dialysis

from

Shock is a state of circulatory dysfunction that occurs from (1) decreased cardiac output and or mal-distribution of regional blood flow and (2) increased metabolic demands with or without impaired oxygen utilization at the cellular level despite adequate oxygen delivery. Cardiac output may be high, low, or normal. The body has compensatory mechanisms to maintain blood pressure through increased heart rate and peripheral vasoconstriction. Hypotension, a late finding in infants and children, occurs when the compensatory mechanisms are failing and cardiorespiratory arrest is imminent. Septic shock is a combination of the three classic types of shock: hypovolemic, cardiogenic, and distributive. Hypovolemia from intravascular fluid losses occurs through capillary leak. Cardiogenic shock results from the myocardial-depressant effects of sepsis. Distributive shock is the result of decreased systemic vascular resistance. The degree to which a patient will exhibit each of these responses is variable. Warm shock occurs in some patients with increased cardiac output and decreased systemic vascular resistance. Cold shock occurs in other patients with decreased cardiac output and elevated systemic vascular resistance. In both cases, perfusion to major organ systems may be compromised. Recent data suggest that, unlike adults in septic shock who present with vasodilation and high cardiac output, newborns and children may have fluid refractory shock and develop progressive myocardial dysfunction. It is important to distinguish between the infection and the host response to the infection, the inflammatory response. The host's immune response, through the actions of the cellular and humoral immune systems, and the reticular endothelium system, prevents the body from developing sepsis in response to breaches in the host defense system. However, this host immune

response produces an inflammatory cascade of highly toxic mediators, including hormones, cytokines, and enzymes. If this inflammatory cascade is uncontrolled, SIRS occurs with subsequent organ and cellular dysfunction from derangement of the microcirculatory system. Microcirculatory dysfunction results in endothelial injury, release of vasoactive substances, changes in cardiovascular tone, mechanical obstruction of the capillary beds from aggregation of cellular elements, and activation of the complement system. At the cellular level there is decreased oxidative phosphorylation secondary to decreased oxygen delivery, anaerobic metabolism secondary to decreased adenosine triphosphate (ATP), glycogen depletion, lactate production, increased cytosolic calcium, activation of membrane phospholipases (further depleting ATP), and release of fatty acids with prostaglandin formation. The inflammatory cascade is initiated by toxins or superantigens. Endotoxin (a lipopolysaccharide), mannose, and glycoprotein components of the cell wall of gram-negative bacteria as well as fungi and yeast bind to macrophages leading to activation and expression of inflammatory genes. Superantigens or toxins associated with gram-positive bacteria, mycobacteria, and viruses activate circulating lymphocytes and initiate an inflammatory mediator cascade. Biochemical responses include the production of arachidonic acid metabolites, release of myocardial depressant factors, release of endogenous opiates, activation of the complement system, as well as the production and release of many other mediators. Arachidonic acid metabolites include (1) thromboxane A2, which causes vasoconstriction and platelet aggregation; (2) prostaglandins, such as PGF2,, which causes vasoconstriction, and PGI,, which causes vasodilation; and (3) leukotrienes that cause vasoconstriction,

bronchoconstriction, and increased capillary permeability. Myocardial depressant factors, tumor necrosis factor-a (TNF), and some of the interleukins cause myocardial depression not only via direct myocardial injury but also by an intracardiac increase in inducible nitric oxide synthase. Endogenous opiates, including P-endorphin, decrease sympathetic activitv, decrease mvocardial contractilitv, and cause vasodilation. Activation of the complement system leads

10

to release of vasoactive mediators that increase capillary permeability, cause vasodilation, and cause activation and aggregation of platelets and granulocytes. Endogenous mediators of sepsis continue to be identified and currently include TNF, interleukin 1 (IL-I), IL-2, IL-4, IL-6, IL- 8, platelet activating factor (PAF), interferon-y, eicosanoids (leukotrienes B4, C4, D4, and E4; thromboxane A2; prostaglandins EL and IL), granulocyte-macrophage colony-stimulating factor, endothelium-derived relaxing factor, endothelin-1, complement fragments C3a and C5a, toxic oxygen radicals, proteolytic enzymes from polymorphonuclear neutrophils, platelets, transforming growth factor-p, vascular permeability factor, macrophage-derived procoagulant and inflammatory cytokine, bradykinin, thrombin, coagulation factors, fibrin, plasminogen activator inhibitor (PAI-I), myocardial depressant substance, endorphin, heat shock proteins, and adhesion molecules (endothelin-derived adhesion molecule [E-selectin]; intercellular adhesion molecule-l [ICAM]; vascular adhesion molecule-1 [VCAM]). The clinical manifestations of sepsis and shock are mediated through the inflammatory cascade. Hypovolemia, cardiac and vascular failure, acute respiratory distress syndrome, insulin resistance, decreased CYP450 activity (decreased steroid synthesis), coagulopathy, and unresolved or secondary infection are all results of the inflammatory cascade. TNF and other inflammatory mediators increase vascular permeability, leading to diffuse capillary leak, decreased vascular tone, and, at the microcirculatory level, an imbalance between perfusion and metabolic demands of the tissue. TNF and IL-1 stimulate the release of proinflammatory and anti-inflammatory mediators causing fever and vasodilatation. Arachidonic acid metabolites lead to the development of fever, tachypnea, ventilation-perfusion abnormalities, and lactic acidosis. Nitric oxide, released from the endothelium or inflammatory cells, is a major contributor to hypotension. Myocardial depression is caused by myocardial depressant factors, TNF, and some interleukins through direct myocardial injury, depleted catecholamines, increased P-endorphin, and production of myocardial nitric oxide. In addition to treating the underlying infection, therapies to augment the host defense, block trigger events, prevent leukocyte endothelial interaction, and

11

inhibit vasoactive substances, cytokines or lipid mediators are being investigated. To date, the results of clinical trials investigating drugs targeting the rnediators of SIRS have been disappointing. Trials have been conducted with anti-endotoxin antibodies, antioxidant compounds, an IL-1 receptor antagonist, IL-1 antibodies, bradykinin-receptor antibodies, cyclo-oxygenase inhibitors, thromboxane

antagonists, PAF antagonists, inhibitors of leukocyte-adhesion molecules, nitric oxide antagonists, anti-TNF antibody, bactericidal permeability increasing protein, and recombinant human activated protein C. Recombinant human activated protein C (drotrecogina) studies have shown improvement in the 28-day survival in adults, but enrollment in a pediatric trial was closed early because of an unfavorable risk-benefit ratio particularly in neonates. The best treatment is early recognition, early antimicrobial therapy, and early goal-directed therapy. 2.5. Clinical Manifestation10 The initial signs and symptoms of sepsis include alterations in temperature regulation (hyperthermia or hypothermia), tachycardia, and tachypnea. In the early stages (hyperdynamic phase), the cardiac output increases in an attempt to maintain adequate oxygen delivery to meet the increased metabolic demands of tissues. As sepsis progresses, cardiac output falls in response to the effects of numerous mediators. Although hypotension (systolic arterial pressure <2 standard deviations below the mean for age) is a late finding in children with sepsis, it is not a criteria for the diagnosis of shock in infants and young children. Other signs of poor cardiac output include delayed capillary refill, diminished peripheral and central pulses, cool extremities, and decreased urine output. Alterations in mental status, including confusion, agitation, lethargy, anxiety, obtundation, or coma, can also be signs of poor cardiac output. Capillary leak develops from altered vascular permeability. Lactic acidosis occurs as shock progresses and is the consequence of increased tissue production and decreased hepatic clearance. Cutaneous lesions seen in septic patients include petechiae, diffuse erythema, ecchymoses, ecthyma gangrenosum, and symmetric peripheral gangrene. Jaundice can be seen either as a sign of infection or as a result of

12

MODS. The patient may also have evidence of focal infection such as meningitis, pneumonia, arthritis, cellulitis, or pyelonephritis. 2.6. Diagnosis10 The diagnosis of sepsis requires SIRS in the presence of proven infection or a clinical picture consistent with infection. An infectious etiology should be sought by culturing clinically appropriate specimens taken from body fluids (blood, urine, cerebrospinal fluid, abscesses, peritoneal fluid, etc.). Infectious disease and intensive care consults are necessary. Cultures take time for incubation and are not always positive. Additional evidence to identify an infectious etiology as the cause of SIRS includes physical examination findings, imaging (chest radiograph with evidence of pneumonia), presence of white cells in normally sterile body fluids, and suggestive rashes such as petechiae and purpura. Affected children should be admitted to an intensive care unit where continuous, close invasive monitoring can be performed, including central venous pressure and arterial blood pressure. Laboratory findings often include evidence of hematologic abnormalities and electrolyte disturbances. Hematologic abnormalities include

thrombocytopenia, prolonged prothrombin and partial thromboplastin times, reduced serum fibrinogen levels and elevated fibrin split products, and anemia. Also, elevated neutrophil and increased immature forms (bands, myelocytes, promyelocytes), vacuolation of neutrophils, toxic granulations, and Dohle bodies can be seen with infection. Neutropenia is an ominous sign of overwhelming sepsis. Electrolyte abnormalities include hyperglycemia as a stress response or hypoglycemia if glycogen reserves are exhausted. Other electrolyte abnormalities include hypocalcemia, hypoalbuminemia, metabolic acidosis, and low serum bicarbonate. Lactic acidosis can occur if there is significant anaerobic metabolism. Renal and liver function may be abnormal if the patient develops MODS. Patients with acute respiratory distress syndrome or pneumonia will have impaired oxygenation (decreased PaO2) and ventilation (increased PaC02). Examination of infected body fluids may reveal neutrophils and bacteria. Some biochemical

13

markers examination such as procalcitonin, CRP, etc, can be used to support the diagnosis of sepsis. Table 2-3 Laboratory indicators of sepsis12 Laboratory Test White blood count Platelet count Findings Leukocytosis /leucopenia Thrombocytosis or thrombocytopenia Comments Endotoxemia may cause leucopenia High value early may be seen as acute phase response; low platelet counts seen in overt DIC Abnormalities can be observed onset of organ failure and without frank bleeding Doubling-indicates acute renal injury Indicates tissue hypoxia Indicates acute hepatocelular injury caused by hypoperfusion Inversely correlated with proinflammatory cytokine levels Acute phase response Differentiates infectious SIRS from noninfectious SIRS

Coagulation cascade

Creatinine level Lactic acid level Liver enzyme level Serum phosphate level C-reactive protein (CRP) level Procalcitonin level 2.7. Management

Protein C deficiency; antithrombin deficiency; elevated Ddimer level; prolonged PT and PTT Elevated from baseline Lactic acid > 4 mmol/L (36mg/dL) Elevated alkaline phosphatase, AST, ALT, bilirubin levels Hypophosphatemia

Elevated Elevated

2.7.1 Initial Resuscitation5 The primary goals of therapy in the first hours following clinical presentation are to maintain oxygenation and ventilation and achieve normal perfusion. Important clinical parameters that are reflective of normal perfusion include: capillary refill < 2 seconds, normal pulses with no differential between the quality of peripheral and central pulses, warm extremities, normal mental status, normal blood pressure for age and appropriate urine output for age.

14

2.7.2 Airway and oxygenation5 Early medical responders (e.g. EMS and transport personnel, ED staff) should ensure a patent airway and appropriate protective airway reflexes are present, especially if there is any alteration in mental status. When any degree of distress or abnormal respiratory function is noted, the patient should be placed on 100% oxygen to ensure maximal oxygen saturation. While specific diagnosis of sepsis is being evaluated, emergency support should include high flow supplemental oxygen and evaluation for further respiratory support for acute respiratory failure, which may be due to acute lung injury or shock. It includes oxygen using non-rebreathing mask, nasal prong CPAP, tracheal tube with CPAP or manual ventilation as per clinical situation. SpO2 of 94% is desirable. Intubation and ventilation is indicated in-patients having hypoxemia not responding to oxygen administration by non-invasive methods, hypotension and/or clinical signs suggestive of myocardial dysfunction or pulmonary edema.12 In addition, myocardial dysfunction, which is often present in children with sepsis, can be partially ameliorated by the application of positive pressure ventilation by achieving a decrease in afterload (provided impairment of preload is not too great). Therefore, early semi-elective intubation and positive pressure mechanical ventilatory support should be strongly considered in this setting.

2.7.3 Fluid resuscitation We recommend the protocolized resuscitation of a patient with sepsis induced shock, defined as tissue hypoperfusion (hypotension persisting after initial fluid challenge or blood lactate concentration 4 mmol/L). This protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending ICU admission. During the first 6 hrs of resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as one part of a treatment protocol: Central venous pressure 812 mmHg Mean arterial pressure (MAP) 65mm Hg

15

Urine output 0.5 ml/kg/hr Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively.14 Early rapid fluid resuscitation is fundamental to septic shock survival. Pre-

load needs to be optimized to improve cardiac output and thus oxygen delivery. Intravenous access may be difficult to achieve in children with poor hemodynamics. In such a case, intraosseous line should be established if three attempts have failed or 90 sec have lapsed.13 Fluid resuscitation is best initiated with rapid infusion of normal saline or Ringers lactate. Recent evidence clearly support the use of crystalloid (normal saline) in pediatric septic shock. There may be a role of colloids (albumin, dextrans, starch and gelatin in saline) in patients with a pre-existing low plasma oncotic pressure state such as protein energy malnutrition, nephrotic syndrome, acute severe burns or liver disease, in patients with malaria and dengue shock syndrome. In hypotensive patients, fluids should be given as rapidly as possible in aliquots of 20 ml/kg using a syringe and a 3-way stopcock and rapid pullpush or pressure bag system to achieve therapeutic goals. In patients with normal blood pressure fluids should be given in aliquots of 20 ml/kg over 1520 min. In a randomized trial that compared slow and fast infusion rate, fast infusion did not result in faster resolution of shock but incidence of pulmonary edema requiring intubation doubled if fluids were given at rate of 40 ml in 15 min, compared to 20 ml over 15 min. Children with septic shock usually require 4060 ml/kg, sometimes up to 90110 ml/kg in the first hour of resuscitation. It may go up to 200 ml in 6 hr or 240 ml in 8 hr in staphylococcal diseases presenting with septic shock, vasodilatory shock or shock due to gastrointestinal sepsis.13 If signs of shock persist despite adequate volume replacement and perfusion of vital organ is jeopardized, inotropic drugs may be used to improve cardiac output. The effects of a particular drug in an individual patient are unpredictable and must be closely monitored. Drugs commonly used in pediatric ICU to increase myocardial contractility include the following:15 a. Dopamine

16

The primary indication for dopamine is the need to increase myocardial contractility after preload restoration. The usual dose is 5-20 mcg/kg/min titrated to desired effect. Dopamine (in doses of more than 5 mcg/kg/min) should preferably be given via central line to prevent ischemic necrosis of the skin. b. Dobutamine It is a selective -1 agonist. The reduction in afterload and improved myocardial performance lowers ventricular filling pressures. The usual dose is 520 mcg/kg/min. It should be not used alone in septic shock due to it could cause further drop in blood pressure. Dopamine or adrenaline can be used to prevent hypotension owing to vasoconstrictive effect. c. Adrenaline (epinephrine) It is used in which dominant hemodynamic feature is peripheral vascular failure, as in septic shock. At higher doses severe vasoconstriction can lead to lactic asidosis and renal splanchnic ischemia. The usual dose is 0.1-1 mcg/kg/min. It should be titrared closely and the minimum dose should be used as required. d. Noradrenaline In severe septic shock with hypotension despite the use of adrenaline secondary to intense vasodilatation, noradrenaline may be useful in increasing peripheral vascular resistance to improve blood pressure. The dose is 0.05-1 mcg/kg/min. 2.7.4 Elimination of Pathogen10 Soon after diagnosed the patient should be administered by initial antibiotics. The preferred antibiotics are those ones that are broad spectrum and are predicted to be able to eliminate the most often gram positive and negative bacteria that cause sepsis. For the initial phase, Ampicilin (200mg/kg/day/iv in 4 dose) combined with aminoglycoside (garamicin 5-7mg/kg/day/iv or amikacin 1520mg/kg/day/iv or netilmicin 5-6 mg/kg/day/iv in 2 dose) are preferred. In a septic shock setting, the use of aminoglycoside should be monitored cautiously due to septic shock is prone to kidney injury, thus another combination is preferred if monitoring aminoglycoside is difficult which is ampicilin with cefotaksim (100

17

mg/kg/day/iv in 3 dose). If there is a suspicion of the presence of an anaerobic bacteria (for instance a focus infection in the abdomen, pelvis, mouth , rectum) then the patient should be administered metronidazole or clindamicin with another antibiotic which is suitable for enteric gram-negative bacteria. 2.7.5 Glycemic control16 Hyperglycemia is a common occurrence in critically ill patients due to peripheral insulin resistance, relative insulin deficiency and impaired glucose metabolism. There have been many studies that have shown as association between elevated glucose and mortality in critically ill children, however none established a causal relationship between untreated hyperglycemia and mortality nor did they show a decrease in mortality with strict glycemic control. Given the ongoing concern regarding the detrimental effects of inducing hypoglycemia with insulin therapy, and studies which have shown poorer outcomes withsignificant glucose variability, we do not recommend the routine use of insulin in hyperglycemic states. Attention should be paid to controlling the amount of glucose administered in the setting of hyperglycemia and the treatment of prolonged hyperglycemia should be reserved for those cases in which the hyperglycemia is causing clinical compromise (in the form of osmotic diuresis or ketoacidosis). 2.7.6 Corticosteroid10 The benefit of corticosteroid in septic shock is still controversial, there are difference in experiment results. Corticosteroid is thought to have benefit if given in the early stadium of sepsis, however has to be administered in the presence of adrenal glandula bleeding. The corticosteroid that is given are metyl prednisolone (30 mg/kg/dose/iv) or dexamethasone (3 mg/kg/dose/iv). Prognosis9 Hospital mortality generally varied little with age, except for the significantly higher rate among infants, who were incurred for 47% of all deaths.

2.8

18

Because hospital mortality varied little with age, the number of deaths per population paralleled the incidence rate, with a high rate in infants that fell dramatically in older children. There was no gender-related difference in hospital mortality. The mortality rate was significantly increased by the severity of the septic process: among the severe sepsis cases the mortality rate was 5%, whereas among the patents with septic shock it was much higher: 53%. The risk of death also increased with increasing number of failing organs, from 3.8% for those with single organ dysfunction to 53.2% for those with four organ systems or more failing.

19

CHAPTER III CASE REPORT

Name Age Sex Address Date of Admission

: MA : 1 year 5months : Male : Jl. Besar Klumpang Kec Hamparan : October 7th 2012

Major Complaint History

: Loss of consciousness : Loss of consciousness was experienced by the patient

since twelve days ago. Loss of consciousness was preceded by seizure. The seizure was experienced for 3 days and frequent, with a duration of 5-10 minutes, involving the whole body with the

eyes directed upwards and the upper and lower limbs rigid and the seizure was preceded with fever. Fever was found and recurrent fever was for the last 3 weeks, with a characteristic of high fever and gone with administration of antipyretic. Diarrhea was not found but there is a history of diarrhea for the last 2 weeks, the frequency is hard to determinate due to the presence of colostomy, with a volume of 200cc/day, blood and mucus was not found. This patient was first admitted to H. Adam Malik General Hospital with chief complaint of abdominal discomfort and emesis on September 18th 2012 and was diagnosed invagination from the Surgery Department and undergone a laparatomy emergency surgery with a result of colostomy. Patient was then transferred to the pediatric ICU on September 27th 2012 based on chief complaint of loss of consciousness.

History of Birth: spontaneous labor, first child, birth weight: 4100 gram, birth length: 50cm, immediate crying (+), cyanosis (-) Feeding History From birth to 6 months From 6 month to 9 month : Breast milk only : Milk Porridge + Breast milk

20

From 9 month to now

: Baby rice + Breast Milk

History of Growth and Development: The patient was able to sit at age 7 month The patient could stand up by himself at age 9 month The patient could walk with guidance since age 11 month

History of Immunization History of previous illness History of previous medications

: Complete for age : ileosecum invagination, gastroenteritis : unclear

Physical Examination : Generalized status Body weight: 8.6 kg, Body length: 81 cm Body weight in 50th percentile according to age: 11.5 kg Body length in 50th percentile according to age: 81 cm Body weight in 50th percentile according to body length: 11.5 kg

BW/BL: 8.6/11.5 x 100% = 74.7 % BW/age: 8.6/11.5 x 100% = 74.7 % BL/ age : 81/81 x 100% = 100 % Presence Status Sensorium : Apathies, Temperature: 38.7C Anemic (-),icteric (-), dyspnea (-), cyanotic (-), edema (-). Body weight (BW): 8.6 kg. Body length (BL): 81 cm CDC: BW/Age = %, BL/Age = %, BW/BL = % Localized status: Head : Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose : NGT (+), nasal canul (+). Ear and mouth: within normal limit.

21

Neck Thorax

: Lymph node enlargement (-) : Symmetrical fusiformis. Chest retraction (+).RR: 62 tpm, regular, crackles (+/+), HR: 146 bpm, regular, murmur (-)., stridor (-)

Abdomen

: Soepel, peristaltic (+), colostomy (+) LLQ. Liver and spleen not palpable

Extremities

: Pulse: 136 bpm, regular, adequate pressure/volume, warm axilla, Capillary Refill Time (CRT) < 3 BP: 110/70 mmHg.

Urogenital

: Male, within normal limit

Physiologic reflexes: KPR (+), APR(+) Pathologic reflexes : Oppenheim (-), Hoffman (-), Babinsky (-), Chaddock (-), Gordon(-), Nuchal rigidity (-)

Laboratory findings: CBC Hemoglobin (Hb) Erytrocyte (RBC) Leukocyte (WBC) Hematocrite Trombocyte (PLT) MCV MCH MCHC Neutrofil Lymphocyte Monocyte Eosinophil Basophil 25/09/2012 13.00 g% 5.14 x 106/mm3 19.91 x 103/mm3 36.60 % 425 x 103/mm3 27/09/2012 9.20 g% 3.73 x 106/mm3 20.53 x 103/mm3 27.60 % 216 x 103/mm3 6/10/2012 10.20 g% 4.50 x 106/mm3 7.62 x 103/mm3 30.30 % 162 x 103/mm3 67.30 fL 22.70 pg 33.70 g% 60.10 % 26.90 % 12.70 % 0.00 % 0.30 % 6/10/2012 7.455 30.3 mmHg 165.9 mmHg 20.9 mmol/L

pH PCO2 pO2 Bicarbonate

71.20 fL 74.00 fL 25.30 pg 24.70 pg 35.50 g% 33.30 g% 68.20 % 82.90 % 12.60 % 7.70 % 19.10 % 9.40 % 0.00 % 0.00 % 0.10 % 0.00 % Blood Gas 25/09/2012 27/09/2012 7.588 7.563 20.7 mmHg 36.7 mmHg 177.4 mmHg 183.3 mmHg 19.4 mmol/L 32.3 mmol/L

22

(HCO3) Total CO2 BE Oxygen saturation

20.0 mmol/L -0.8 mmol/L 99.4%

33.4 mmol/L 9.5 mmol/L 98.9%

21.8 mmol/L 2.3 mmol/L 99.3% 6/10/2012 6.6 mg/dL 125 mEq/L 3.9 mEq/L 4.2 mEq/L 104 mEq/L 1.28 mEq/L 2/10/2012 35.92 ng/mL 2/10/2012 4.9 mmol/L Normal value

Calcium (Ca) Natrium (Na) Kalium (K) Phosphor Chloride (Cl) Magnesium (Mg)

Procalcitonin Lactic Acid

Electrolyte 26/09/2012 27/09/2012 6.6 mg/dL 7.1 mg/dL 124 mEq/L 132 mEq/L 1.7 mEq/L 2.1 mEq/L 1.4 mEq/L 2.1 mEq/L 90 mEq/L 96 mEq/L 1.15 mEq/L 1.04 mEq/L Other test 26/09/2012 28/09/2012 47.27 ng/mL 3.12 ng/mL 27/09/2012 28/09/2012 1.5 mmol/L 1.0 mmol/L Result

HST PT INR APTT TT Fibrinogen D-dimer Liver Total Bilirubin Direct Bilirubin ALP AST/SGOT ALT/SGPT Renal Ureum Creatinin Uric Acid

1.12 x 1.14 1.14 x 1.21 x 329 mg/dL 1031 ng/dL 0.30 mg/dL 0.17 mg/dL 105 U/L 124 U/L 30 U/L 9.10 mg/dL 0.26 mg/dL 3.3 mg/dL Result

150-400 <500 <1 0-0.2 <281 <38 <41 <50 0.24-0.41 <7.0 Normal value Transparent <200 10-40 <32

CSF analysis Colour LDH Total Protein Leucocyte Eritrocyte

transparant 62 U/L 12.00 mg/dL 0.004 x 103/uL 0.001 x 103/uL

23

Glucose pH PMN MN Radiologic Findings :

60 mg/dL 8.0 75% 25%

32-82 7-8

a. Thorax x-ray (AP) on September 28th 2012 Intepretation of x-ray : No enlargement of the heart Sinus and diaphragm normal Both hilus normal No sign of infiltrate on both lungs Normal vascular and bronchus pattern Conclusion: no signs of abnormality of the heart and lungs b. d CT-Scan on October 3rd 2012

Intepretation: Infratentorial : the 4th ventricle and the cerebellum seems normal.

24

Supratentorial : there seems to have a hypodense area on the right and left the fronto-temporo-parietal There seems to be no mass or any midline shifting Ventricular system and cortical sulci normal There seems to be no pathologic enhancement

Conclusion: Encephalitis

Working Diagnosis: Encephalitis + Post laparatomy a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Sepsis

Management: Head elevation 30o P: - IVFD D5% NaCl 0.9% 20 gtt/i E: Diet F100: 140cc/3hours/OGT + mineral mix 2,8cc Ampicillin inj. 450mg/6 hours/iv Cefotaxime 250mg/6 hours/iv Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 Metronidazole inj. 75mg/8 hours/iv Farmadol inj. 100mg Morphine inj. 8.5mg in 50cc D5% (tapering off dose 0.5cc/hour) Zinc 1x20mg Folic acid 1x1mg Multivitamin without Fe 1 x Cth1/2 Diagnostic Planning: Complete blood count Anemia profile Electrolyte profile Random blood glucose Blood Gas Analysis Septic workout Culture urine, blood, feces and CSF

25

Follow Up 8th October 2012 S O Deterioration of consciousness(+), fever(+), diarrhea(-), seizure(-) CNS syst : Unstable, GCS 14 (E4V4M6) Head: Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). CV syst : Stable, HR: 138 bpm, reg, murmur (-), BP: 93/61mmHg, MAP: 71mmHg , UOP: 680cc/24 hours(3.27cc/kgBB/hour) Resp syst : Unstable, Thorax: SF, epigastrial retraction (+),RR: 50 tpm, reg crackles (-/-) H: Nasal flare (-), Nasal canul: 1/2-1 L/i. Met. syst : Unstable Abdomen: soepel, peristaltic(+)N, stoma(+), feses(+), albumin: 2.7 Ca/Na/K/Cl/Mg/Ph :7.8/132/4.2/106/6.6/1.50/4.5 Infec. syst: Stable, fever (-), T: 38.1oC, Procalcitonin: 1.18 MS syst : Stable, post surgery wound: dry Encephalitis + Post laparatomy (D-19) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Sepsis with unstable CNS and metabolic system - Head elevation 30o - Fluid requirements: 1100cc-1200cc/day P: - IVFD D20% = D5% NaCl(364cc) + D40%(136cc) > 15gtt/i - Aminofusin 7cc/hour E: Diet F100: 95cc/3hours/OGT - Ampicillin inj. 450mg/6 hours/iv (D-5) - Cefotaxime 250mg/6 hours/iv (D-5) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-12) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D1-2) - Metronidazole inj. 75mg/8 hours/iv (D-12) - Farmadol inj. 100mg - Morphine inj. 8.5mg in 50cc D5% (tapering off dose 0.5cc/hour) - Zinc 1x20mg (D-12) - Folic acid 1x1mg (D-12) - Multivitamin without Fe 1 x Cth1/2 (D-9) - Ca Gluconas 4.3cc in 3.3cc D5% within 20

26

- Albumin 25% 9.6cc - Check Ca and albumin levels post correction 9th October 2012 S O Deterioration of consciousness(+), fever(-), diarrhea(-), seizure(-), ruam kemerahan pada bekas colostomy CNS syst : Unstable, GCS 14 (E4V4M6) Head: Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). CV syst : Stable, HR: 150bpm, reg, murmur (-), pulse: 150 bpm, p/v adequate, BP: 100/70mmHg, MAP: 80mmHg, CVC placed (D-9), UOP: 920cc/24 hours (4.43cc/kgBB/hour) Resp syst : Stable, Thorax: SF, epigastrial retraction (+),RR: 44 tpm, reg ,crackles (-/-) H: Nasal flare (-) Nasal canul: 1/21 L/i. Met. syst : Unstable, Abdomen: soepel, peristaltic(+)N, stoma(+), feses(+), Ca: 8.9 Infec. syst: Stable, fever (-), T: 36.8oC MS syst : Stable, post surgery wound: dry Encephalitis + Post laparatomy (D-20) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Irritant Contact Dermatitis + Sepsis with unstable CNS, and metabolic system - Head elevation 30o - Fluid requirements: HS+20%op besar: 1060cc/hr P: - IVFD D20% = D5% NaCl(364cc) + D40%(136cc) > 15gtt/i - Aminofusin 7cc/hour E: Diet F100: 95cc/3hours/OGT - Ampicill;in inj. 450mg/6 hours/iv (D-6) - Cefotaxime 250mg/6 hours/iv (D-6) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-13) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-13) - Metronidazole inj. 75mg/8 hours/iv (D-13) - Farmadol inj. 100mg - Morphine inj. 8.5mg in 50cc D5% (tapering off dose 0.5cc/hour) (D10) - Zinc 1x20mg (D-13) - Folic acid 1x1mg (D-13) - Multivitamin without Fe 1 x Cth1/2 (D-10) - Pediasure 95cc/3 hours/NGT

27

- Gentamicin zalf - Check Procalcitonin and lactic acid levels 10th October 2012 S O Fever(+), deterioration of consciousness(+), diarrhea(-), seizure(-), ruam kemerahan pada bekas colostomy CNS syst : Unstable, GCS 14 (E4V4M6) Head: Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). CV syst : Stable, HR: 140bpm, reg, murmur (-), pulse: 140bpm, p/v adequate, BP: 100/50mmHg, MAP: 66mmHg, CVC placed (D-10), UOP: 1220cc/24 hours (5.7cc/kgBB/hour) Resp syst : Stable, Thorax: SF, epigastrial retraction (+),RR: 36 tpm, reg ,crackles (-/-) H: Nasal flare (-), Nasal canul: 1/2-1 L/i. Met. syst : Unstable, Abdomen: soepel, peristaltic(+)N, stoma(+), feces(+): vol.50cc , Infec. syst: Stable, fever(+), T: 38.9oC, Lactic acid: 2.4, Pro: 0.82 MS syst : Stable, post surgery wound: dry Encephalitis + Post laparatomy (D-21) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Irritant Contact Dermatitis + Sepsis ec Acinetobacter baumanii with unstable CNS, and metabolic system - Head elevation 30o - O2 -1 L/i - Fluid requirements: HS+20%op besar: 1060cc/hr P: - IVFD D20% = D5% NaCl(364cc) + D40%(136cc) + KCl (10mEq) + Ca Gluconas (10cc) > 11gtt/i - Aminofusin 11cc/hour E: Pediasure: 75cc/3hours/OGT - Metronidazole inj. 75mg/8 hours/iv (D-14) - Ampicillin inj. 450mg/6 hours/iv (D-7) - Cefotaxime 250mg/6 hours/iv (D-7) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-14) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-14) - Farmadol inj. 100mg - Morphine inj. 0.5cc/hour (D-11) - Zinc 1x20mg (D-14) - Folic acid 1x1mg (D-14)

28

S O

Multivitamin without Fe 1 x Cth1/2 (D-11) Gentamicin zalf Pediasure 75cc/3 hours/NGT Check urinalysis, feces analysis, and electrolyte 11th October 2012

Fever(+), deterioration of consciousness(+), diarrhea(-), seizure(-), ruam kemerahan pada bekas colostomy CNS syst : Unstable, GCS 14 (E4V4M6) Head: Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). CV syst : Stable, HR: 160bpm, reg, murmur (-), pulse: 160bpm, t/v adequate, BP: 110/60mmHg, MAP: 90mmHg, CVC placed (D-11), UOP: 660cc/24 hours (3.27cc/kgBB/hour) Resp syst : Stable, Thorax: SF, epigastrial retraction (+),RR: 36 tpm, reg ,crackles (-/-) H: Nasal flare (-), Nasal canul: 1/2-1 L/i. Met. syst : Unstable,Abdomen: soepel, peristaltic(+)N, stoma(+), feces(+): vol.150cc , Ca/Na/K/Cl/Mg/Ph : 8.1/128/3.7/104/1.9/4.0 Urinalysis : within normal limit Fecal analysis : within normal limit Infec. syst: Stable, fever(+), T: 38oC, MS syst : Stable, post surgery wound: dry Encephalitis + Post laparatomy (D-21) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Irritant Contact Dermatitis + Sepsis ec Acinetobacter baumanii with unstable CNS, and metabolic system - Head elevation 30o - O2 -1 L/i - Fluid requirements: HS+20%op besar: 1060cc/hr P: - IVFD D20% = D5% NaCl(364cc) + D40%(136cc) + KCl (10mEq) + Ca Gluconas (10cc) > 11gtt/i - Aminofusin 11cc/hour E: Pediasure: 80cc/3hours/OGT - Amikacin 220mg/hr in 50cc D5% within 30 - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-14) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-14)

29

S O

Farmadol inj. 100mg Morphine inj. 0.5cc/hour (D-12) Zinc 1x20mg (D-15) Folic acid 1x1mg (D-15) Multivitamin without Fe 1 x Cth1/2 (D-12) Gentamicin zalf Pediasure 80cc/3 hours/NGT Citrizine 1x2.5mg 12th October 2012

Deterioration of consciousness(+), fever(-), diarrhea(-), seizure(-), ruam kemerahan pada bekas colostomy CNS syst : Unstable, GCS 14 (E4V4M6) Head: Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). CV syst : Stable, HR: 130bpm, reg, murmur (-), pulse: 130bpm, p/v adequate, BP: 100/60mmHg, MAP: 73mmHg, CVC placed (D-12), UOP: 600cc/24 hours (2.9cc/kgBB/hour) Resp syst : Stable,Thorax: SF, epigastrial retraction (+),RR: 30 tpm, reg ,crackles (-/-) H: nasal flare(-), Nasal canul: 1/2-1 L/i. Met. syst : Unstable,Abdomen: soepel, peristaltic(+)N, stoma(+), feces(+): vol.130cc , Infec. syst: Stable, fever(+), T: 38oC MS syst : Stable, post surgery wound: dry Encephalitis + Post laparatomy (D-22) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Irritant Contact Dermatitis + Sepsis ec Acinetobacter baumanii with unstable CNS, and metabolic system - Head elevation 30o - O2 -1 L/i - Fluid requirements: HSB P: - IVFD D20%: 8gtt/ - Aminofusin 5%: 3.5cc/hour E: Pediasure: 100cc/3hours/OGT - Amikacin 160mg/hr in 50cc D5% within 30(D-2) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-16) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-16) - Omeprazole 8mg/8 hour/iv

30

S O

Farmadol inj. 100mg Morphine inj. 0.5cc/hour (D-13) Citrizine 1x2.5mg Zinc 1x20mg (D-16) Folic acid 1x1mg (D-16) Multivitamin without Fe 1 x Cth1/2 (D-13) Gentamicin zalf Pediasure 100cc/3 hours/NGT Resomal 50-100cc/times diarrhea Candistatin drop 3 x gttII Check FBC, LFT, RFT, Electrolyte, procalcitonin, lactic acid 13th October 2012

Fever(+), deterioration of consciousness(+), diarrhea(+), seizure(-), ruam kemerahan pada bekas colostomy CNS syst : Unstable, GCS 15 (E4V5M6) Head: Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). CV syst : Stable, HR: 146bpm, reg, murmur (-), pulse: 146bpm, p/v adequate, BP: 100/60mmHg, MAP: 73mmHg, CVC placed (D-13), UOP: 960cc/24 hours (4.76cc/kgBB/hour) Resp syst : Stable, Thorax: SF, epigastrial retraction (+),RR: 30 tpm, reg ,crackles (-/-) H: Nasal flare(-), Nasal canul: 1/2-1 L/i. Met. syst : Unstable,Abdomen: soepel, peristaltic(+)N, stoma(+),feces(+):vol.250cc,Albumin:3.4, Ca/Na/K/Cl/Mg/Ph :8.5/133/4/102/8.9/1.82/3.4 Infec. syst: Stable, fever(+), T: 39oC, lactic acid: 2.0, Pro: 0.81 MS syst : Unstable, post surgery wound: dry CBC : Hb/RBC/WBC/PLT/HT = 6 3 3 8.2/3.7x10 /9.94x10 /374x10 /25.5 MCV/MCH/MCHC/RDW = 68.9/22.2/32.2/29.1 N/L/M/E/B = 57.7/29.7/11/1.3/0.3 Encephalitis + Post laparatomy (D-23) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Irritant Contact Dermatitis + Sepsis ec Acinetobacter baumanii with unstable CNS, and metabolic system - Head elevation 30o - O2 -1 L/i - IVFD D5% = D5% NaCl(500cc)+ KCl (10mEq) + Ca Gluconas (10cc) > 7gtt/I (micro)

31

- Amikacin 160mg/hr in 50cc D5% within 30(D-3) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-17) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-17) - Omeprazole 8mg/8 hour/iv - Farmadol inj. 100mg - Citrizine 1x2.5mg - Folic acid 1x1mg - Multivitamin without Fe 1 x Cth1/2 (D-14) - Gentamicin zalf - Pediasure 110cc/3 hours/NGT - Resomal 50-100cc/times diarrhea - Candistatin drop 3 x gttII - PRC transfusion 50cc 14th October 2012 S O Fever(+), deterioration of consciousness(+), diarrhea(+), seizure(-) Sens : CM Head : T: 37oC W: 8.6kg

Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose: NGT, nasal canule. Ear and mouth: within normal limit. Thorax : Symmetrical fusiformis, retraction(-), HR: 126bpm, reg, murmur (-), RR: 22 tpm, reg ,crackles (-/-) Abdomen: Soepel, peristaltic(+)N, stoma(+), feces(+) Extremity: Pulse: 126bpm, reg, CRT<3 BP: 100/60mmHg A Encephalitis + Post laparatomy (D-24) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Sepsis ec Acinetobacter baumanii - Head elevation 30o - O2 -1 L/i - IVFD D5% = D5% NaCl(500cc)+ KCl (10mEq) + Ca Gluconas (10cc) > 7gtt/I (micro) - Amikacin 160mg/hr in 50cc D5% within 30(D-4) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-18) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-18)

32

S O

Omeprazole 8mg/8 hour/iv Paracetamol 3x100mg Citrizine 1x2.5mg Folic acid 1x1mg Multivitamin without Fe 1 x Cth1/2 (D-15) Gentamicin zalf Pediasure 110cc/3 hours/NGT Resomal 50-100cc/times diarrhea Candistatin drop 3 x gttII Transfusi PRC Wash II (50cc) Check FBC 15th October 2012 T: 39.2oC

Fever(+), deterioration of consciousness(+), diarrhea(+), seizure(+) Sens : CM Head : W: 8.6kg

Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose: NGT, nasal canule. Ear and mouth: within normal limit. Thorax : Symmetrical fusiformis, retraction(-), HR: 120bpm, reg, murmur (-), RR: 20 tpm, reg ,crackles (-/-) Abdomen: Soepel, peristaltic(+)N, stoma(+), feces(+) Extremity: Pulse: 120bpm, reg, CRT<3 BP: 100/60mmHg A Encephalitis + Post laparatomy (D-24) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Sepsis ec Acinetobacter baumanii - Head elevation 30o - O2 -1 L/i - IVFD D5% NaCl 7gtt/I (micro) - Amikacin 160mg/hr in 50cc D5% within 30(D-5) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-19) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-19) - Omeprazole 8mg/8 hour/iv - Paracetamol 3x100mg - Citrizine 1x2.5mg - Folic acid 1x1mg - Multivitamin without Fe 1 x Cth1/2 (D-16)

33

S O

Gentamicin zalf Pediasure 110cc/3 hours/NGT Resomal 50-100cc/times diarrhea Candistatin drop 3 x gtt II 16th October 2012 T: 38.2oC

Fever(+), seizure(+) Sens : CM Head : W: 8.6kg

Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose: NGT, nasal canule. Ear and mouth: within normal limit. Thorax : Symmetrical fusiformis, retraction(-), HR: 122bpm, reg, murmur (-), RR: 24 tpm, reg ,crackles (-/-) Abdomen: Soepel, peristaltic(+)N, stoma(+), feces(+), Liver and Spleen: unpalpable Extremity: Pulse: 122bpm, reg, CRT<3 BP: 100/60mmHg Encephalitis + Post laparatomy (D-25) a/i Ileosecal invagination + Bronchopneumonia + Moderate malnutrition + Sepsis ec Acinetobacter baumanii - Head elevation 30o - O2 -1 L/i - IVFD D5% NaCl 7gtt/I (micro) - Amikacin 160mg/hr in 50cc D5% within 30(D-6) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-20) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-20)s - Omeprazole 8mg/8 hour/iv - Paracetamol 3x100mg - Citrizine 1x2.5mg - Folic acid 1x1mg - Ferry syr 1x CthI - Gentamicin zalf - Pediasure 110cc/3 hours/NGT - Resomal 50-100cc/times diarrhea - Candistatin drop 3 x gtt II - Check FBC, electrolyte, blood gas, procalcitonin, lactic acid, CRP 17th October 2012

34

S O

Fever(+), seizure(+), diarrhea Sens : CM Head : T: 37.8oC W: 8.85kg

Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose: NGT, nasal canule. Ear and mouth: within normal limit. Thorax : Symmetrical fusiformis, retraction(-), intercostals space clearly seen, HR: 124bpm, reg, murmur (-), RR: 24 tpm, reg ,crackles (-/-) Abdomen: Soepel, peristaltic(+)N, stoma(+), feces(+), Liver and Spleen: unpalpable Extremity: Pulse: 124bpm, reg, CRT<3 BP: 100/60mmHg CBC : Hb/RBC/WBC/PLT/HT = 12/4.63x106/14.15x103/74x103/34.1 MCV/MCH/MCHC/RDW = 73.7/25.9/35.2/25.3 N/L/M/E/B = 73.4/17.3/8.9/0.1/0.3 Electrolyte: Ca/Na/K/Cl/Mg/Ph : 8.6/133/2.7/106/8.9/1.75/2.8 Procalcitonin: >100.00 3.8 Lactic acid : positive CRP : pH/pCO2/pO2/HCO3/TCO2/BE/SaO2= Blood gas : 7.403/29.9/104.1/18.2/19.1/-5.5/ 97.6 Encephalitis + Post laparatomy (D-25) a/i Ileosecal invagination + Bronchopneumonia + Severe Malnutrition type marasmus + Sepsis ec Acinetobacter baumanii - Head elevation 30o - O2 -1 L/i - IVFD D5% NaCl 7gtt/I (micro) - Amikacin 160mg/hr in 50cc D5% within 30(D-7) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-21) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-21) - Ketorolac inj. 2mg/6 hour/iv - Ranitidine 9mg/8 hour/iv - Paracetamol 3x100mg - Citrizine 1x2.5mg - Folic acid 1x1mg - Ferry syr 1x CthI - Gentamicin zalf - Pediasure 110cc/3 hours/NGT - Resomal 50-100cc/times diarrhoea - Candistatin drop 3 x gtt II - Diet F100 160cc/3 hours NGT + Mineral mix 3.2cc

35

18th October 2012 S O Fever(-), seizure(-), diarrhea(+) Sens : CM Head : T: 37.5oC W: 8.5kg

Face: old man face (+) Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose: NGT, nasal canule. Ear and mouth: within normal limit. Thorax : Symmetrical fusiformis, retraction(-), intercostals space clearly seen, HR: 122bpm, reg, murmur (-), RR: 22 tpm, reg ,crackles (-/-) Abdomen: Soepel, peristaltic(+)N, stoma(+), feces(+), Liver and Spleen: unpalpable Extremity: Pulse: 124bpm, reg, CRT<3 BP: 110/80mmHg Encephalitis + Post laparatomy (D-28) a/i Ileosecal invagination + Severe Malnutrition type marasmus + Sepsis ec. Acinetobacter baumanii - Head elevation 30o - O2 -1 L/i - IVFD D5% NaCl 7gtt/I (micro) - Amikacin 160mg/hr in 50cc D5% within 30(D-8) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-22) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-22) - Ketorolac inj. 2mg/6 hour/iv - Check blood gas 19th October 2012 Fever(-), seizure(-), diarrhea(+) Sens : CM T: 37.5oC W: 8.5kg

S O

36

Head

Face: old man face (+) Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose: NGT, nasal canule. Ear and mouth: within normal limit. Thorax : Symmetrical fusiformis, retraction(-), intercostals space clearly seen, HR: 160bpm, reg, murmur (-), RR: 38 tpm, reg ,crackles (+/+) Abdomen: Soepel, peristaltic(+)N, stoma(+), feces(+), Liver and Spleen: unpalpable Extremity: Pulse: 160bpm, reg, CRT<3 BP: 150/120mmHg Blood gas pH/pCO2/pO2/HCO3/TCO2/BE/SaO2= 7.376/30.1/190.7/17.3/18.2/-6.9/ 99.4 Encephalitis + Post laparatomy (D-29) a/i Ileosecal invagination + Severe Malnutrition type marasmus + Sepsis ec. Acinetobacter baumanii - Head elevation 30o - O2 -1 L/i - IVFD D5% NaCl 7gtt/I (micro) - Amikacin 160mg/hr in 50cc D5% within 30(D-9) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-23) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-23) - Ketorolac inj. 2mg/6 hour/iv - Carbamazepin 3x15mg (D-1) 20th October 2012 Fever(+), seizure(-), diarrhea(-) Sens : CM Head : T: 37.9oC W: 8.75kg

S O

Face: old man face (+) Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose: NGT, nasal canule. Ear and mouth: within normal limit. Thorax : Symmetrical fusiformis, retraction(-), nasal flare (+) intercostals space clearly seen, HR: 120bpm, reg, murmur (-), RR: 40 tpm, reg ,crackles (+/+) Abdomen: Soepel, peristaltic(+)N, stoma(+), feces(+), Liver and Spleen: unpalpable

37

Extremity: Pulse: 160bpm, reg, CRT<3 BP: 130/100mmHg

Encephalitis + Post laparatomy (D-30) a/i Ileosecal invagination + Severe Malnutrition type marasmus + Sepsis ec. Acinetobacter baumanii - Head elevation 30o - O2 -1 L/i - IVFD D5% NaCl 7gtt/I (micro) - Amikacin 160mg/hr in 50cc D5% within 30(D-10) - Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-24) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-24) - Ketorolac inj. 2mg/6 hour/iv - Carbamazepin 3x15mg (D-2) 21th October 2012 Fever(-), seizure(-), diarrhea(+) Sens : CM Head : T: 37oC W: 8.75kg

S O

Face: old man face (+) Eye: light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-). Nose: NGT, nasal canule. Ear and mouth: within normal limit. Thorax : Symmetrical fusiformis, retraction(-), nasal flare (-), intercostals space, clearly seen,HR: 122bpm, reg, murmur (-), RR: 42 tpm, reg ,crackles (+/+) Abdomen: Soepel, peristaltic(+)N, stoma(+), feces(+), Liver and Spleen: unpalpable Extremity: Pulse: 160bpm, reg, CRT<3 BP: 150/120mmHg Encephalitis + Post laparatomy (D-31) a/i Ileosecal invagination + Severe Malnutrition type marasmus + Sepsis ec. Acinetobacter baumanii

38

Head elevation 30o O2 -1 L/i IVFD D5% NaCl 7gtt/I (micro) Amikacin 160mg/hr in 50cc D5% within 30(D-11) Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-25) - Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20 (D-25) - Ketorolac inj. 2mg/6 hour/iv - Carbamazepin 3x15mg (D-3) -

39

CHAPTER 4 DISCUSSION & SUMMARY

4.1

Discussion MA, male, 1 year 5 months was admitted to Pediatrics Department of RSUP

HAM and was diagnosed with encephalitis with bronchopneumonia, moderate malnutrition, and sepsis with unstable CNS, metabolic, and musculoskeletal system and was a post laparatomy pasien due to ileoseptal invagination. The diagnosis was established based on history taking, clinical manifestations, radiology and laboratory findings. From history taking and clinical manifestations patient experienced loss of consciousness, seizure, recurrent fever and diarrhoea. The treatment given were IVFD D5% NaCl 0.9%, Diet F100: 140cc/3hours/OGT + mineral mix 2,8cc, Ampicillin inj. 450mg/6 hours/iv , Cefotaxime 250mg/6 hours/iv, Phenitoin inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20, Phenobarbital inj. MD 25mg/12 hours/iv in 10cc NaCl 0.9% within 20, Metronidazole inj. 75mg/8 hours/iv, Farmadol inj. 100mg, Morphine inj. 8.5mg in 50cc D5% (tapering off dose 0.5cc/hour), Zinc 1x20mg, Folic acid 1x1mg, multivitamin without Fe 1 x Cth1/2

Sepsis may develop as a complication of a localized infection or may follow colonization and mucosal invasion by virulent pathogens. Patients at risk for sepsis include infants, children with serious injuries, children on chronic antibacterial therapy, malnourished children, and children with chronic medical problems.

In this case, MA is 1 year 5 month boy, with encephalitis, bronchopneumonia, moderate malnutrition and is post laparatomy patient.

According to the site of infection and microbiologic etiology, the majority of infections causing sepsis were respiratory (64%), followed by digestive and

40

urinary tract infections (18% and 12% respectively). From the microbiologic aspect, gram-negative bacteria caused the majority of infections that evolved with sepsis, with Escherichia coli and Klebsiella pneumoniae being the most frequent pathogens. The most common Gram-positive infecting organism was

Staphylococcus aureus. Atypical pathogens were identified in a minority of patients. Pseudobacteremia may be associated with contaminated heparin flush solutions, intravenous solutions, albumin, cryoprecipitate, and infusion

equipment. Infections with gram-negative bacterla (e.g., Escherichia coli, Pseudomonas, Acinetobacter, Klebsiella, Enterobacter, Serratia) and fungi (e.g., Candida, Aspergilus most often occur in immunocompromised and hospitalized patients colonized with these organisms. Contaminants include water-borne organisms such as Acinetobacter baumanii, Pseudomonas aeruginosa, and Serratia

The site of infection in this case is thought to be in the CNS with diagnose of encephalitis. However, patient was also diagnosed with bronchopneumonia. From the culture that was done there were a few microorganism that was found. From the blood Acinetobacter baumanii was isolated. From the cerebrospinal fluid Proteus mirabilis was isolated by BACTEC and Acinetobacter baumanii was isolated from culture. And there was no growth of microorganism from the urine.

The initial signs and symptoms of sepsis include alterations in temperature regulation (hyperthermia or hypothermia), tachycardia, and tachypnea. As sepsis progresses, cardiac output falls in response to the effects of numerous mediators. Signs of poor cardiac output include delayed capillary refill, diminished peripheral and central pulses, cool extremities, and decreased urine output. Alterations in mental status, including confusion, agitation, lethargy, anxiety, obtundation, or coma, can also be signs of poor cardiac output.

In this case, the patient experienced frequent alternation of tempreture, some days normal but somedays could have a tempreture reaching 38.90. This phenomenom also occurred with the respiratory rate. The patient had CRT

41

<3,warm extremities and no decrease in urine output. However, there was alteration in mental status. The diagnosis of sepsis requires SIRS in the presence of proven infection or a clinical picture consistent with infection. An infectious etiology should be sought by culturing clinically appropriate specimens taken from body fluids (blood, urine, cerebrospinal fluid, abscesses, peritoneal fluid, etc.). In this case the criteria of SIRS that was present is hyperthermia, tachypnea, and also there was leucocytosis . And the infectious etiology was cultured from CSF and blood. Giving rise to Acinetobacter baumanii from the blood and from the CSF Proteus mirabilis and Burkholderia cepacia was isolated. Laboratory findings often include evidence of hematologic abnormalities and electrolyte disturbances. Hematologic abnormalities include

thrombocytopenia, prolonged prothrombin and partial thromboplastin times, reduced serum fibrinogen levels and elevated fibrin split products, and anemia. Electrolyte abnormalities include hyperglicemia, hypocalcemia,

hypoalbuminemia, metabolic acidosis, and low serum bicarbonate. Lactic acidosis can occur if there is significant anaerobic metabolism. Some biochemical markers examination such as procalcitonin, CRP, etc, can be used to support the diagnosis of sepsis. In this case, hematologic abnormalities that was seen were elevated Ddimer and there was evidence once of thrombocytopenia. Electrolyte abnormalities that was discovered were hypocalcemia, hyponatremia,

hypokalemia, hypoalbuniemia. There were no evidence of metabolic asidosis, however low serum bicarbonate was seen. The levels of lactic acid, procalcitonin and CRP was seen. And there was evidence of elevation of ALT and AST. The mainstay of the treatment of sepsis include airway patency with adequate oxygenation, fluid resuscitation, elimination of pathogen, treatment of hyperglycemia, corticosteroid and other treatment according to organ dysfunction.

42

MA, was treated with oxygenation, fluid, and for the elimination of pathogen the patient was given empiric antibiotic such as amphicilin, ceftriaxone , and metronidazol. And from the result of sensitivity test amikasin was then the antibiotic of choice.

4.2. Summary MA, male, 1 year 5 months was admitted to Pediatrics Department of RSUP HAM and was diagnosed with encephalitis with bronchopneumonia, moderate malnutrition, and sepsis with unstable CNS, metabolic, and musculoskeletal system and was a post laparatomy pasien due to ileoseptal invagination. Patient is still hospitalized in Adam Malik General Hospital.

43

REFERENCES 1. Starke R.J., Tuberculosis. In: Gershon A.A., Hotez J.P., Katz L.S., Krugmans Infectious Disease of Children 11th edition. Philadelphia. 2004. P. 731-762. 2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associates cost of care. Crit Care Med. 2001;29(7): 1303-10. 2. Kissson N, Carcillo JA, Espinosa V, Argent A, Devictor D, Madden M, et al. World federation of pediatric intensive care and critical care societies: global sepsis initiative. Pediatr Crit Care Med. 2011;12(5):494-503. 3. Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, et al. Nationwide trends of severe sepsis in the 21st century (2000-2007). Chest. 2011;140(5): 1223-31. 4. Goldstein B, Giroir B, Randolph A. International pediatrics sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005:6; 413-40. 5. El-wiher N, Cornell, TT, Kissoon N, Shanley TP. Management and Treatment Guidelines for Sepsis in Pediatrics Patients. The Open Inflammation Journal. 2011;4:101-9 6. Gebara BM. Values for systolic blood pressure. Pediatr Crit Care Med. 2005: 6; 500 (author reply-1). 7. Watson RS, Carcillo JA. Scope and epidemiology of pediatric sepsis. Pediatr Crit Care Med. 2005;6:3-5. 8. The Global Burden of Disease: 2004 Update. Geneva, Switzerland, World Health Organization, 2008. 9. Militaru M, Martinovici D. Our Experience in Pediatric Sepsis. Jurnalul Pediatrului. 2005;8:26-31. 10. Enrione MA, Powell KR. Sepsis, Septic Shock, and Systemic Inflammatory Response Syndrome. In: Behrman RE, Kliegman RM, Jenson HB, Stanton BF,

44

Ziteli BJ, Davis HW, editors. Nelson Textbook of Pediatrics. 18th ed. Philadelphia: Saunders; 2007:1094-99 11. Soedarmo SS, Garna H, Hadinegoro SR, Satari HS. Buku Ajar Infeksi dan Pediatri Tropis. 2nd ed. Jakarta: IDAI; 2012:358-363. 12. Somasetia DH. Tatalaksana Awal Sepsis Berat dan Syok Sepsis Anak. In: Ali M, Dimyati Y, Adriansyah R, Trisnawati Y, editors. Tatalaksana Awal Kegawatan pada Bayi dan Anak. Medan: IDAI-Sumut;38-61. 13. Singhi S, Argent AC, Baranwal AK, Santhanam I. Septic shock: Management in emergency department with available resources. Journal of Pediatric Infectious Diseases. 2009;4:8598. 14. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36:296-327. 15. Khilnani P. Clinical management guidelines of pediatric septic shock. Indian J Crit Med. 2005;9(3): 164-172. 16. Singal M, Mizuno Y, Skippen P, Kissoon N. Sepsis in the pediatric intensive care unit. Journal of Pediatric Infectious Diseases. 2009;4:99-106.