PICU II

PICU II Allison M. Chung, Pharm.D., BCPS, FCCP Auburn University Harrison School of Pharmacy Mobile, Alabama

PICU II

PICU II Allison M. Chung, Pharm.D., BCPS, FCCP Auburn University Harrison School of Pharmacy Mobile, Alabama

ACCP Updates in Therapeutics® 2015: Pediatric Pharmacy Preparatory Review Course 1-211

PICU II

Learning Objectives 1. Interpret arterial blood gas results, and apply them to patient management. 2. Explain the rationale for stress ulcer prophylaxis in the pediatric intensive care unit (PICU), and discuss the therapeutic options. 3. Describe the risk of gastrointestinal bleeds in the PICU, and determine the best strategy for management. 4. Outline the therapeutic options for and management of acute respiratory distress syndrome in children. 5. Compare and contrast hospital-acquired pneumonia and ventilator-associated pneumonia in the PICU, and discuss recommended prevention strategies. 6. Define status epilepticus, and determine the optimal treatment strategies for it. 7. Discuss the mechanisms of diabetic ketoacidosis and the optimal management strategies.

Self-Assessment Questions Answers and explanations to these questions can be found at the end of this chapter. 1. A.S. is a 3-year-old boy (weight 13 kg) who has just been admitted to the pediatric intensive care unit (PICU) for pneumonia. He is not currently intubated. His most recent arterial blood gas (ABG) is a pH of 7.48, Pco2 of 30 mm Hg, and bicarbonate of 22 mEq/L. Which primary acid-base disorder is most consistent with A.S.’s laboratory data? A. Metabolic acidosis. B. Respiratory acidosis. C. Metabolic alkalosis. D. Respiratory alkalosis. Questions 2–4 pertain to the following case: T.N. is a 5-year-old girl (weight 20 kg) who is in the PICU for status epilepticus (SE). She seized twice for about 15 minutes before cessation of the seizures with benzodiazepines. Her current laboratory values include the following: sodium 137 mEq/L, potassium 4.2 mEq/L, bicarbonate 18 mEq/L, chloride 100 mEq/L, blood urea nitrogen (BUN) 20 mg/dL, serum creatinine (SCr) 0.3 mg/dL, and lactic acid 120 mg/dL. Her ABG includes a pH of 7.3 and a Pco2 of 30 mm Hg.

2. Which primary acid-base disorder is most consistent with T.N.’s laboratory and clinical data? A. Metabolic acidosis. B. Respiratory acidosis. C. Metabolic alkalosis. D. Respiratory alkalosis. 3. Which is the most likely reason for T.N.’s acid-base disorder? A. Hypoxia secondary to the seizures. B. Hyperglycemia as a reflex response to the seizures. C. Renal dysfunction secondary to this patient’s seizure disorder. D. Lactic acidosis caused by muscle breakdown after the seizures. 4. Which best represents the calculated anion gap for T.N.? A. 5. B. 11. C. 23. D. 40. 5. N.M. is a 3-month-old (weight 4 kg, height 24 inches [60 cm]) African American infant admitted to the PICU for dehydration and sepsis. He was born full term with a normal vaginal delivery and has no significant medical history. He was electively intubated in the PICU 2 days ago because of altered mental status and vasopressor requirements. He is currently on milrinone 0.25 mcg/kg/minute, midazolam 0.1 mg/kg/hour, and fentanyl 1 mcg/kg/hour. His most recent laboratory values include the following: sodium 140 mEq/L, potassium 3.5 mEq/L, chloride 105 mEq/L, bicarbonate 22 mEq/L, BUN 20 mg/ dL, SCr 0.7 mg/dL, glucose 90 mg/dL, and international normalized ratio (INR) 1.82. Which medication would be best for stress ulcer prophylaxis in this patient? A. Ranitidine 4 mg intravenously every 6 hours. B. Pantoprazole 4 kg intravenously daily. C. Sucralfate 5 mL nasogastrically every 6 hours. D. No stress ulcer prophylaxis needed.


PICU II

6. S.R. is a 10-year-old (weight 25 kg) female patient who has been in the PICU for more than 2 weeks. She has a medical history of retinopathy of prematurity, laryngomalacia, cerebral palsy, developmental delay, and decreased GI motility. She was born prematurely at 30 weeks and spent several weeks in the neonatal ICU for feeding and growth. During this PICU stay, she has been on dopamine and dobutamine for sepsis and has received 2 days of methylprednisolone. She had a previous GI bleed that required endoscopic sclerotherapy and a generalized convulsive SE event requiring phenytoin therapy. Which is the most likely risk factor for GI bleeding in S.R.? A. Born prematurely. B. History of SE. C. History of corticosteroid use. D. Previous GI bleed. 7. T.K. is a 5-year-old girl (weight 20 kg) with acute respiratory distress syndrome (ARDS) admitted to the PICU 2 days ago. Her medical history includes several acute otitis media episodes. The most recent episode was about 1 week ago. She is currently intubated on a fraction of inspired oxygen (Fio2) of 0.8 (80% O2) and a positive end expiratory pressure (PEEP) of 12 cm H2O. She has no wheezing but is positive for rales on the left upper chest area. Which would be the best treatment option for this patient? A. Methylprednisolone 20 mg intravenously every 6 hours. B. Albuterol 2.5 mg nebulized every 6 hours. C. Tidal volume of 120 mL. D. Inhaled nitric oxide at 20 ppm.

8. R.M., a 1-year-old female infant (weight 11 kg), has been in the PICU for 72 hours for respiratory distress and acute mental status changes. She has a medical history of autism, bronchopulmonary dysplasia, and gastroesophageal reflux disease. Intubated since admission, she was initiated on ranitidine for GI prophylaxis. She is also on midazolam 0.2 mg/ kg/hour and fentanyl 2 mcg/kg/hour. She receives chlorhexidine washes every 12 hours around her oral mucosa area, and her bed is elevated 35 degrees. The hospital infection control supervisor is reviewing R.M. for her risk of ventilator-associated pneumonia (VAP). Which other practice is best to prevent VAP in this patient? A. Daily sedation holidays. B. Extubation earlier and often. C. Low PEEP ventilation. D. Proton pump inhibitor for further stress ulcer prophylaxis. 9. A.P. is a 2-month-old female infant (weight 3.5 kg) who has been in the PICU for 14 days for respiratory distress secondary to late-stage group B Streptococcus sepsis. She has already received a 14-day course of antibiotics for group B Streptococcus sepsis. She was recently intubated and was stable on 2 L/minute of high flow nasal cannula, but overnight, her oxygen saturation decreased to 92%. Her sputum is thick, yellowish, and creamy. Her morning CBC (complete blood cell count) includes a white blood cell (count) (WBC) of 3 x 103 cells/mm3 (78 polymorphonuclear leukocytes, 12 band neutrophils, 9 lymphocytes, and 3 monocytes), hemoglobin of 9 g/dL, hematocrit of 30%, and platelet count of 100,000/mm3. Her vital signs include a temperature of 97°F, heart rate (HR) of 180 beats/ minute, respiratory rate (RR) of 24 breaths/minute, and blood pressure (BP) of 100/60. Her chest radiograph shows new infiltrates, and her radiograph yesterday was read with increasing consolidation. Sputum cultures are sent, and antibiotics are initiated. Which antibiotic is best for this patient? A. Amoxicillin 90 mg/kg/day orally every 12 hours. B. Ampicillin 400 mg/kg/day every 6 hours plus gentamicin 5 mg/kg/day. C. Ceftazidime 150 mg/kg/day every 6 hours. D. Clindamycin 40 mg/kg/day every 6 hours.


PICU II

10. L.T. is a 14-year-old male adolescent (weight 40 kg) with a history of seizure disorder. He was at a friend’s house during the weekend and forgot his seizure medications of topiramate and tiagabine. He got home from his friend’s house and began having a generalized clonic status epilepticus (GCSE) event. His mother administered 5 mg of rectal diazepam and called EMS (emergency medical services). Diazepam stopped his seizure during transport, but on admission to the PICU, he began seizing again. The EMS personnel were able to place a peripheral line before the seizure. Which would be the best option to manage his GCSE now? A. Another 5-mg dose of rectal diazepam. B. Lorazepam 4 mg intravenously. C. Topiramate 50 mg orally. D. Midazolam continuous infusion at 0.1 mg/kg/ hour. 11. R.M. is a 7-month-old boy (weight 8 kg) admitted to the PICU for new-onset GCSE. He has no pertinent medical history and had a normal vaginal birth. He has a social history of two sisters in day care and a dog and a cat. He presented to the PICU seizing for 10 minutes. He was given two doses of lorazepam 0.8 mg intravenously, but they did not terminate the seizures. Which would be the next best option for this patient? A. Diazepam rectally 1 mg. B. Phenytoin 160 mg intravenously over 2 minutes. C. Fosphenytoin 160 mg phenytoin equivalents (PE) intravenously over 6 minutes. D. Valproic acid 320 mg intravenously over 10 minutes. 12. S.S. is a 7-year-old girl (weight 20 kg) who has been having polydipsia, polyuria, and nausea/vomiting for the past week. She has no significant medical history. On admission to the emergency department (ED), her Accu-Chek glucose reading was 1005 mg/ dL, and she had Kussmaul breathing. She is slightly obtunded, has extremely dry mucous membranes and skin tenting. She received 100 mL of 0.9% normal saline in the ED, after which she was admitted to the PICU. Laboratory values were pending on her transfer to the PICU. Which would be the best initial management for this patient?

A. Obtain an ABG to learn her pH value. B. Rehydrate with 300 mL of 0.9% normal saline over 1 hour. C. Rehydrate with 250 mL of 0.9% normal saline with 20 mEq of potassium over 1 hour. D. Initiate insulin continuous intravenous infusion at 0.1 unit/kg/hour. 13. D.K. is a 9-year-old boy (height 57 inches [145 cm], weight 45 kg) with type 1 diabetes mellitus who has been sick for the past week with nausea, vomiting, and dehydration. He is on an insulin pump, but it stopped working 2 days ago, and he did not tell anyone. He has been admitted to the PICU with a pH of 7.0, bicarbonate 5 mEq/L, and Pco2 32 mm Hg. His blood glucose initially was 1050 mg/dL. One hour later, it was 903 mg/dL, and 1 hour after that, it was 780 mg/dL. His temperature is 101°F, RR is 12 breaths/minute, HR is 120 beats/minute, and BP is 135/80 mm Hg. Which factor places D.K. at most risk of cerebral edema? A. High glucose. B. pH of 7.0. C. Decrease in glucose from 1050 mg/dL to 800 mg/dL. D. His use of the insulin pump.

Abbreviations ABG Arterial blood gas ALI Acute lung injury ARDS Acute respiratory stress syndrome DKA Diabetic ketoacidosis ED Emergency department GCSE Generalized clonic status epilepticus HAP Hospital-acquired pneumonia MRSA Methicillin-resistant Staphylococcus aureus PICU Pediatric intensive care unit RSV Respiratory syncytial virus SE Status epilepticus VAP Ventilator-associated pneumonia


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I. Acid-Base Disorders A. Background 1. Acid-base disorders are common in the PICU. 2. Use ABGs. B. Explain Normal Values for ABGs. 1. pH a. Expresses the degree of acidity of the body b. pH less than 6.7 or greater than 7.7 is incompatible with life. 2. Pco2 (carbon dioxide) a. Partial pressure of carbon dioxide (in blood) b. Acts as a “respiratory acid” c. The rate and depth of respiratory ventilation vary to allow for excretion of CO2. d. Increases in CO2 elimination or hyperventilation, decreased Pco2 e. Decreased ventilation (hypoventilation); decreases in CO2 elimination, which increases Pco2 f. Can respond or change rapidly 3. Carbonic acid/bicarbonate a. Carbonic acid regulated by Pco2 b. Bicarbonate regulated by kidneys (metabolic) c. Most abundant extracellular buffer d. Bicarbonate is calculated on ABG and is measured with serum electrolytes. 4. Sao2: Saturation of arterial oxygen Table 1. Normal Blood Gas Values Arterial Blood

Mixed Venous Blood

pH

7.40 (7.35–7.45)

7.38 (7.33–7.43)

P o2

80–100 mm Hg (10.6–13.3 kPa)

35–40 mm Hg (4.7–5.3 kPa)

Sao2

95% (0.95)

70%–75% (0.70–0.75)

Pco2

35–45 mm Hg (4.7–6.0 kPa)

45–51 mm Hg (6.0–6.8 kPa)

HCO3

22–26 mEq/L (22–26 mmol/L)

24–28 mEq/L (24–28 mmol/L)

HCO3 = bicarbonate; Pco2 = partial pressure of carbon dioxide; Po2 = partial pressure of oxygen; Sao2 = saturation of arterial oxygen. From: Devlin JW, Matzke GR. Acid-base disorders. In: DiPiro JT, ed. Pharmacotherapy: A Pathophysiological Approach, 9th ed. New York: McGraw-Hill, 2014:800.

C. Metabolic 1. Acidosis a. pH less than 7.4; severe if pH less than 7.2 b. Sign/symptoms i. Hyperventilation ii. Kussmaul breathing iii. Flushing iv. Rapid HR v. Wide pulse pressures vi. Nausea/vomiting (cause rather than effect?) ACCP Updates in Therapeutics® 2015: Pediatric Pharmacy Preparatory Review Course 1-215

PICU II

vii. Hyperkalemia (extracellular shift of potassium) viii. Confusion/lethargy c. Anion gap i. AG (mEq/L) = (Na+ + K+) – (Cl- + HCO3-). Many references do not include potassium in the calculation because of its minor effect. ii. Quantifies unmeasured anions iii. Normal: 3–11 mEq/L iv. Causes of elevated anion gap (a) M-ethanol (b) U-remia (c) D-KA (d) P-araldehyde (e) I-ron or isoniazid (f) L-actic acid (g) E-thylene glycol (h) S-alicylic acid d. Hyperchloremic metabolic acidosis i. Normal anion gap ii. Causes (a) GI bicarbonate losses (e.g., diarrhea) (b) Biliary or pancreatic drainage (c) Drugs (1) Normal saline resuscitation or isotonic intravenous fluids (2) Calcium chloride (3) Magnesium sulfate (diarrhea) (d) Renal tubular acidosis (e) Acid ingestion (f) Dilutional acidosis – Rapid infusion of 0.9% sodium chloride (NaCl) 2. Alkalosis a. pH greater than 7.4; severe if pH greater than 7.6 b. Signs/symptoms i. Muscle weakness/cramping ii. Hypokalemia (intracellular shift of potassium) iii. Dizziness iv. Cardiac arrhythmias v. Neuromuscular irritability vi. Mental confusion vii. Paresthesia c. Causes of metabolic alkalosis i. Hypochloremia and hypobicarbonatemia (chloride responsive) (a) Vomiting (b) Nasogastric suctioning (c) Aggressive diuresis (d) Cystic fibrosis ii. Chloride resistant (a) Mineralocorticoid excess (b) Severe potassium depletion (c) Bartter syndrome (d) Gitelman syndrome ACCP Updates in Therapeutics® 2015: Pediatric Pharmacy Preparatory Review Course 1-216

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iii. Milk alkali syndrome iv. Large blood or plasma protein transfusions D. Respiratory 1. Acidosis a. Usually life threatening b. Lungs are unable to excrete carbon dioxide. c. Signs/symptoms i. Altered mental status ii. Abnormal behavior iii. Seizures iv. Stupor v. Coma vi. Headache vii. Papilledema viii. Abnormal reflexes d. Causes of respiratory acidosis i. Head injury ii. Infection iii. SE iv. Stroke v. Cardiac arrest vi. Chronic lung disease/severe pneumonia vii. ARDS viii. Brain stem or cervical cord injuries 2. Alkalosis a. Decrease in Paco2 b. Signs/symptoms i. Light-headedness ii. Confusion iii. Decreased cognition iv. Syncope v. Seizures vi. Nausea/vomiting vii. Cardiac arrhythmias viii. Hypokalemia c. Causes of respiratory alkalosis i. Shock ii. Anxiety iii. Tachypnea iv. Pain v. Fever vi. Brain tumors vii. Head trauma viii. Ingestions ix. Hypoxemia x. Asthma


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Table 2. Acid-Base Disturbances Disorder

pH

Primary Disturbance

Compensatory Response

Metabolic acidosis

↓

↓ HCO3

↓ Pco2

Metabolic alkalosis

↑

↑ HCO3

↑ Pco2

Respiratory acidosis

↓

↑ Pco2

↑ HCO3

Respiratory alkalosis

↑

↓ Pco2

↓ HCO3

E. Compensation 1. Respiratory compensation a. Occurs in minutes to hours b. Lungs compensate to achieve balance in the body. c. For metabolic acidosis i. Increase RR to increase carbon dioxide elimination. ii. Decreases Paco2 d. For metabolic alkalosis i. Hypoventilation to retain carbon dioxide ii. Increases Paco2 2. Metabolic compensation a. Kidneys regulate/compensate to achieve balance. b. Occurs in days c. Respiratory alkalosis i. Compensation begins after 6–12 hours of respiratory alkalosis. ii. Increased renal excretion of bicarbonate; decreased sodium bicarbonate d. Respiratory acidosis i. Compensation begins after 12–24 hours of respiratory acidosis. ii. Increased renal reabsorption of bicarbonate – Increased serum bicarbonate F. Mixed Acid-Base Disorders 1. Respiratory acidosis and metabolic acidosis a. Cardiac arrest b. Chronic lung disease and shock 2. Respiratory alkalosis and metabolic alkalosis – Mechanical ventilation and vomiting/nasogastric suctioning or blood transfusions 3. Metabolic acidosis and respiratory alkalosis a. Advanced liver disease b. Salicylate toxicity c. Pulmonary-renal syndromes 4. Metabolic alkalosis and respiratory acidosis – Chronic obstructive lung diseases and salt restriction/ diuretics or glucocorticoids G. Management Strategies 1. Almost always involves correcting the underlying cause


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2. Acute severe metabolic acidosis, hyperchloremic acidosis: Alkali therapy not often recommended because depends on oxidative conversion to bicarbonate. Most critically ill patients have impaired oxidative conversion. a. Sodium acetate, sodium citrate, sodium lactate b. Intravenous sodium bicarbonate 3. Metabolic alkalosis a. Usually treat the underlying cause. i. Discontinue offending agents. ii. Correct potassium/chloride deficit if present. b. Acetazolamide 4. Respiratory acidosis – Often mechanical ventilation 5. Respiratory alkalosis a. Usually mild, and no treatment involved b. Adjusting mechanical ventilation • Obtain ABG and electrolytes at same time • Verify that calculated HCO3 on ABG and measured bicarbonate from serum electrolytes are similar (within 2 mEq/L)

Assess pH < 7.4 or > 7.4

Acidosis pH < 7.4

Alkalosis pH > 7.4

↑Pco2

↓HCO3

↓Pco2

↑HCO3

RESPIRATORY ACIDOSIS

METABOLIC ACIDOSIS

RESPIRATORY ALKALOSIS

METABOLIC ALKALOSIS

Calculate anion gap Figure 1. Algorithm for interpreting acid-base disorders.


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II. GASTROINTESTINAL Bleed/Stress Ulcer Prophylaxis A. Gastrointestinal (GI) Bleed 1. Introduction/background a. Up to 25% of critically ill infants and children may develop upper GI bleed or perforation. b. Microscopic bleeding versus overt bleeding 2. Diagnosis of GI bleed – Endoscopy 3. Signs/symptoms of GI bleed a. Hematemesis or “coffee-ground” emesis b. Melena c. Hematochezia d. Nausea/vomiting e. Hypotension f. Shock 4. Risk factors for/causes of GI bleed a. Critical illness b. Peptic ulcer disease c. Esophagitis d. Erosive disease e. Neoplasms f. NSAID (nonsteroidal anti-inflammatory drug) or corticosteroid use 5. Treatment options for GI bleed a. Initially, hemodynamic stabilization and acute correction of fluid status i. Crystalloids – 0.9% NaCl (normal saline) infusions ii. Colloids – Blood products b. Endoscopic treatment options i. Thermocoagulation ii. Sclerotherapy iii. Hemoclipping and ligation c. Pharmacotherapy i. Proton pump inhibitors (a) Usually intravenously (b) Continuous infusions (c) May require long-term use (d) See GI chapter for specific dosing. ii. Histamine-2 (H2)-antagonists are not recommended. iii. Octreotide – Somatostatin is not always recommended. 6. Complications of GI bleed – Rebleeding B. Stress Ulcers or Stress-Related Mucosal Disease (SRMD) or Stress-Related Mucosal Bleeding 1. In the PICU a. Stress ulcers can increase the length of ICU stay. b. Increased costs c. Increased mortality 2. Definition of stress ulcers or SRMD a. Superficial lesions usually in the mucosa of the stomach that occur after periods of stress b. May lead to ulceration and bleeding 3. Diagnosis of stress ulcers a. For diagnosis of ulcers, see the “Gastroenterology/Hepatology” chapter. ACCP Updates in Therapeutics® 2015: Pediatric Pharmacy Preparatory Review Course 1-220

PICU II

b. Stress ulcer is similar to other ulcers except that a stressful situation is involved such as a PICU stay, which increases acid. 4. Pathophysiology of stress ulcers a. Changes in gastric blood flow after stress resulting in hypoperfusion b. Increased mucosal permeability c. Increased concentrations of intragastric hydrogen ions and pepsin d. Decreased GI motility e. Reperfusion can result in further damage. Goal-directed therapy for shock has decreased incidence. f. No defense mechanisms left to protect gastric intestinal mucosa 5. Risk factors for stress ulcers (* = independent risk factor) a. Respiratory failure (need for mechanical ventilation greater than 48 hours)* b. Coagulopathy (INR greater than 1.5, platelet count less than 50,000/mm3)* c. Shock* d. Trauma* e. Pediatric Risk of Mortality (PRISM) score of 10 or higher f. Hypotension g. Sepsis h. Hepatic failure i. Acute renal failure j. High-dose corticosteroids k. Severe burn l. Head injury m. Traumatic spinal cord injury n. Major surgery o. Prolonged ICU admission p. History of GI bleed C. Treatment Options for Stress Ulcer Prophylaxis 1. Gastric acid pH of 4 or more is recommended to decrease incidence of gastric bleeding or stressrelated mucosal damage a. Enteral feeding b. Pharmacotherapy


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Table 3. Pharmacotherapy Options for Stress Ulcer Prophylaxis Drug/Route

Formulation

Doses Neonates

H2RAs:

Infants

Children

10–20 q6– 12h

20–40 q6h

mg/kg/day

Cimetidine

Oral

Oral IV

Ranitidine

Oral IV

Famotidine

PPIs:

5–10 q8–12h

1–3 q8–12h

0.5 QD 1 or 2 q12h

2–4 (prophylaxis) 4–8 (treatment) BID/QD 2–4 q6–8 1–3 months: 0.5 QD > 3 months to 1 year: 1 BID > 1 year: 1 or 2 BID 0.5–1 q12h

Renal adjustments necessary Drug-drug interactions Quick onset Cost-effective

mg/kg/day

Esomeprazole

Oral IV

0.5 QD

0.7–3.3 0.5 QD

Total daily dose: 10 or 20 mg (> 12 years)

0.7–3.3 QD May use q6–8h to maintain gastric pH >5

Total daily dose: 5 to < 10 kg: 5 mg 10 to < 20 kg: 10 mg > 20 kg: 20 mg

Omeprazole

Oral

Omeprazole/ bicarbonate

Oral

Same as omeprazole dosing above

Lansoprazole

Oral

0.2–0.3 QD

Pantoprazole

Comments

Oral IV

0.2–2 QD

0.7–3 QD

1.2

5–11 years: 20 or 40 mg QD (total daily dose) 0.8–1.6

Greater efficacy for bleeding and ulcers Increased risk of pneumonia or Clostridium difficile QD dosing No renal adjustments


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Table 3. Pharmacotherapy Options for Stress Ulcer Prophylaxis (continued) Drug/Route

Formulation

Doses Neonates

PPIs:

Infants

Children

Comments

40–80 q8h

Not as efficacious as the other agents; often adjuvant therapy

mg/kg/day

Sucralfate

Oral

BID = twice daily; h = hour(s); H2RA = histamine-2 receptor antagonist; IV = intravenous; PPI = proton pump inhibitors; q = once; QD = once daily.

2. Controversy or risks regarding stress ulcer prophylaxis a. Pneumonia b. Absorption of medications 3. Length of treatment: Discontinue once risk factors are resolved. Patient Case 1. G.I., a 7-year-old boy (weight 25 kg), is in the PICU for fever, increased emesis of unknown reason, increased work of breathing, and wheezing. His medical history includes asthma and gastroesophageal reflux disease. He was intubated on presentation to the ED after he did not respond to several doses of albuterol, methylprednisolone 50 mg intravenously, and magnesium sulfate 3 g intravenously. On the patient’s presentation to the PICU, the nurse reports red-tinged secretions after suctioning and coffee-ground nasogastric output. His laboratory values include potassium 3.1 mEq/L, SCr 1.1 mg/dL, hemoglobin 10.5 g/dL, and hematocrit 35%. Which is the best initial option for treating this patient? A. Octreotide 25 mcg intravenously x 1. B. Ranitidine 25 mg intravenously every 6 hours. C. Pantoprazole 20 mg intravenously once daily. D. Sucralfate 1 g orally every 8 hours.

III. Acute Respiratory Distress Syndrome A. Background/Epidemiology of ARDS in Pediatric Patients 1. In addition, acute lung injury (ALI) 2. Few definitive trials of ARDS in pediatric patients a. More studies in adults but still not a plethora b. Many questions on whether pediatric ARDS is similar to adult ARDS and whether the information from adults can be transposed to pediatric patients 3. Overall incidence fairly low but mortality high in pediatric patients a. Prevalence is 2–12.8 per 100,000 person-years. b. Mortality 22%–35% 4. Often associated with other underlying disease a. 64%–75% have a preexisting illness. b. Usually pneumonia and sepsis ACCP Updates in Therapeutics® 2015: Pediatric Pharmacy Preparatory Review Course 1-223

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B. Definition/Criteria of ARDS 1. Onset within 72 hours of hypoxemia and radiographic changes, or within 1 week, according to European Society of Intensive Care 2. Acute bilateral infiltrates on chest radiography 3. Hypoxemia a. The ratio of the partial pressure of oxygen in arterial blood to the fraction of inspired oxygen (Pao2/Fio2, or PF ratio) is less than 200 for ARDS. b. Less than 300 for ALI 4. Noncardiogenic pulmonary edema based on an assessment of the left atrial filling pressure by means of a wedged pulmonary artery catheterization or clinical assessment C. Pathophysiology of ARDS 1. Exudative a. Sloughing of alveolar epithelial cells b. Increased permeability of epithelial and endothelial barriers c. Buildup of protein-rich edematous fluid in the interstitium and alveoli d. Influx of macrophages and neutrophils e. Increased other proinflammatory and anti-inflammatory mediators. Infants lack some of the proinflammatory response. f. Inactivation of surfactant g. Infants have impaired pathogen and alveolar fluid clearance. 2. Proliferative a. Interleukin-1 stimulates production of extracellular matrices by fibroblasts. b. Up-regulation of procoagulant pathways 3. Fibrotic a. Extracellular fibrin deposition b. Leads to decreased blood flow in pulmonary vasculature c. Increased pulmonary dead space D. Risk Factors for ARDS 1. Direct lung injury a. Pneumonia b. Aspiration of gastric content c. Inhalational injury d. Pulmonary contusion e. Pulmonary vasculitis f. Drowning 2. Indirect lung injury a. Sepsis b. Severe trauma or shock c. Burns d. Acute pancreatitis e. Head injury f. Drug overdose g. Transfusion E. Course of ARDS 1. Greatly varies by patient 2. Acute or exudative phase: Usually first week ACCP Updates in Therapeutics® 2015: Pediatric Pharmacy Preparatory Review Course 1-224

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3. Subacute phase: About 2 weeks later 4. Chronic phase: More than 14 days from onset F. Management Goals for ARDS 1. Decreased morbidity and mortality 2. Decreased days of mechanical ventilation 3. Promote quicker recovery 4. Maintain long-term pulmonary and neurologic function G. Treatment Strategies for ARDS 1. Mechanical ventilation a. Tidal volume – Volume of air inhaled or passively exhaled during a normal respiratory breath i. Lower tidal volumes – Goal of 6 mL/kg is standard of care in adult ARDS but not as well established in pediatric patients. ii. In pediatric ARDS studies, the mean tidal volume that improved outcomes was around 8 mL/ kg. b. Positive end expiratory pressure (PEEP) i. Moderate to high PEEP – Standard of care in adults but not as well established in pediatric patients ii. PEEP probably very individualized c. High-frequency oscillator ventilation i. May improve survival and is unlikely to cause harm ii. No definitive studies, but it is becoming more commonplace 2. Surfactant a. Standard of care for neonates with respiratory distress syndrome (see Respiratory Distress Syndrome in Neonatology chapter) b. One international multicenter study of calfactant in pediatric patients with ALI or ARDS was terminated early because of futility. c. Has been shown to improve oxygenation and mortality but no differences in duration of ventilation, length of PICU stay, or length of overall hospitalization d. Best to administer 48 hours after onset of ARDS/ALI 3. Bronchodilators a. Albuterol b. Racemic epinephrine c. Inhaled nitric oxide i. Improvement in oxygenation ii. However, no other clinical outcome benefits 4. Diuretics/colloids – Oncotic manipulation a. Maintain fluid balance in the lungs – Prevent vasogenic pulmonary edema b. Prevent vasogenic pulmonary edema 5. Glucose control a. Hypoglycemia risks far outweigh any potential benefit of tight glucose control. b. More studies still needed for definitive answers 6. Mucolytics a. Supportive therapy b. Inhaled hypertonic saline (3% NaCl, 7% NaCl) c. Inhaled sodium bicarbonate (0.5–1 mEq/mL) d. Acetylcysteine e. Dornase alfa (Pulmozyme) ACCP Updates in Therapeutics® 2015: Pediatric Pharmacy Preparatory Review Course 1-225

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7. Corticosteroids a. Use remains controversial. b. Early versus late phase use 8. Extracorporeal membrane oxygenation (ECMO) - Survival rate for ARDS and ECMO is 54%–70%. Patient Case 2. D.P. is an 8-month-old male infant (weight 6 kg) with a medical history of bronchopulmonary dysplasia, for which he is on furosemide and hydrocortisone at home. He is now in the PICU for ARDS and on mechanical ventilation, with an Fio2 of 40%, a PEEP of 7, and a respiratory rate of 24 breaths/minute. He is currently on albuterol, furosemide, hydrocortisone (stress dosed), and sodium bicarbonate inhalations. D.P. is still not moving air well and sounds tight. The resident asks you for the best, most economical therapeutic option to add that is available in the pharmacy. Which is the best reply? A. Surfactant. B. Nitric oxide. C. Albumin. D. Methylprednisolone.

IV. Hospital-Acquired pneumonia/Ventilator-Associated Pneumonia A. Introduction/Background 1. Hospital-acquired pneumonia/ventilatory-associated pneumonia (HAP/VAP) is one of the most common infections acquired by children in the PICU. VAPs: 5.2%–9.6% or 2.1–11.6 cases/1000 ventilator-days 2. Increases risk of mortality 3. Increases length of stay 4. Increases ventilator time 5. Increases overall medical expenditures Table 4. Pneumonia Classification and Risk Factors Type of Pneumonia

Definition

Risk Factors

Hospital acquired (HAP)

Develops > 48 hours after hospital admission and was not incubating at admission

• • • • • • • • • • •

Prior antibiotic exposure Witnessed aspiration COPD, ARDS, or coma Administration of acid reducing medications Supine position Enteral nutrition, NG tube Reintubation, tracheostomy, or patient transport Head trauma, intracranial pressure monitoring Younger age Genetic syndromes or other comorbidities Immunosuppressant drugs


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Table 4. Pneumonia Classification and Risk Factors (continued) Type of Pneumonia

Definition

Risk Factors

Ventilator associated (VAP)

Develops > 48 hours after intubation and mechanical ventilation

• • • • • •

Similar risk factors as above and: Mechanical ventilation > 3 days Neuromuscular blockade Treated with GI motility drugs ↑ PEEP Bronchoscopy

COPD = chronic obstructive pulmonary disease; NG = nasogastric.

B. Pathophysiology/Classification of HAP/VAP 1. Pathophysiology similar to that of community-acquired pneumonia; patients stressed and immunocompromised, which decreases defense system 2. VAP – Results from mechanical ventilation increasing susceptibility to bacterial invasion of the pulmonary mucosa a. Aspiration of secretions can occur. b. Colonization of the lung/GI tract c. Use of contaminated equipment or unsterile medications C. Causative Organisms 1. HAP a. Early – Occurs during the first 4 days of hospitalization i. Viruses (e.g., respiratory syncytial virus [RSV], influenza) ii. Moraxella catarrhalis iii. Haemophilus influenzae iv. Streptococcus pneumoniae v. MSSA (methicillin-sensitive Staphylococcus aureus) vi. Escherichia coli vii. Klebsiella viii. Enterobacter spp. b. Late i. Viruses ii. Gram-negative bacilli (a) Pseudomonas aeruginosa (b) Klebsiella pneumoniae (extended-spectrum ß-lactamase positive) (c) Acinetobacter spp. (d) Legionella (e) S. aureus and methicillin-resistant S. aureus (MRSA) (f) Fungi (includes yeast) 2. VAP a. MRSA b. P. aeruginosa c. Acinetobacter spp. D. Signs/Symptoms of Pneumonia: See Table 5. Also, refer to the “Pulmonary” Chapter.


PICU II

E. Diagnosis of Pneumonia: See Table 5. Also, refer to the “Pulmonary” chapter F. Treatment 1. Empiric therapy based on the most likely organisms a. Early onset i. Third-generation cephalosporin plus vancomycin ii. Ampicillin/sulbactam b. Late onset i. Ceftazidime or cefepime plus aminoglycoside ii. Carbapenem plus aminoglycoside iii. Quinolone plus aminoglycoside iv. Piperacillin/tazobactam plus aminoglycoside v. Vancomycin or linezolid 2. Duration usually 7–10 days G. Complications/Outcomes 1. Increased morbidity 2. Longer duration of mechanical ventilation 3. Pleural effusion – Parapneumonic effusions: A type of pleural effusion that can occur after a pneumonia, lung abscess, or bronchiectasis a. Uncomplicated effusions b. Complicated effusions c. Empyemas i. Empyema is the most common focal complication of pneumococcal pneumonia. ii. Defined as a grossly purulent effusion iii. Should be considered when fluid in the pleural space is accompanied by fever (even low grade) and leukocytosis after 4–5 days of appropriate antibiotic therapy iv. Pleural fluid with frank pus bacteria or a pH of 7.1 or less indicates empyema. v. Demands aggressive and complete drainage, usually through chest tube insertion vi. The effusion is an empyema if bacteria are present on Gram stain, the pH is 7.1 or less, and there are more than 100,000 neutrophils/mm3. vii. Both chest thoracostomy tube drainage with the addition of fibrinolytic agents and videoassisted thoracoscopic surgery have been shown to be effective methods of treatment. 4. Lung abscess 5. Respiratory failure 6. Shock/multiorgan failure 7. Exacerbation of comorbid illness H. VAP Prevention 1. The Institute for Healthcare Improvement (IHI) has recommendations for preventing VAPs (VAP bundles) a. Elevated head of bed: A multivariable analysis of risk factors showed a 67% reduction in VAP among patients maintained in a 30–45 degree head of bed elevation during the first 24 hours of mechanical ventilation. b. Daily sedation holidays and assessment of readiness for extubation c. Stress ulcer prophylaxis d. Oral hygiene 2. Other prevention recommendations a. In-line suctioning ACCP Updates in Therapeutics® 2015: Pediatric Pharmacy Preparatory Review Course 1-228

PICU II

b. c. d. e. f.

Hand hygiene Selective decontamination Avoid unplanned extubation and reintubation. Cuffed endotracheal tube with in-line or subglottic suctioning Avoid H2-blockers or proton pump inhibitors for patients not at risk of a stress ulcer.

Table 5. Specific Site Algorithms for Clinically Defined Pneumonia Radiology

Signs/Symptoms/Laboratory

Two or more serial chest radiographs with at least one of the following

For ANY PATIENT, at least one of the following: • Fever (>38°C or >100.4°F) • Leukopenia (12,000 WBC/mm3) • For adults >70 years old, altered mental status with no other recognized cause

• New or progressive and persistent infiltrate • Consolidation • Cavitation • Pneumatoceles, in infants ≤1 year old NOTE: In patients without underlying pulmonary or cardiac disease (e.g., respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary edema, or chronic obstructive pulmonary disease), one definitive chest radiograph is acceptable.

and at least two of the following: • New onset of purulent sputum, or change in character of sputum, or increased respiratory secretions, or increased suctioning requirements • New onset or worsening cough, or dyspnea, or tachypnea • Rales or bronchial breath sounds • Worsening gas exchange (e.g., O2 desaturations (e.g., PaO2/FiO238.4°C or >101.1°F) or hypothermia (