1. January 2014 Stanford University Loren D. Sacks, MD

2. Ouch!! The most common thoracic injury seen in children is: a. Pulmonary contusion b. Aortic rupture c. Clavicular fracture d. Myocardial contusion e. Tracheal disruption

3. You’ve got the shakes… A 6-year-old with renal failure develops seizures after 6 days in the PICD. Her medications include fentanyl, meperidine, digoxin, atracurium, meropenem, and dobutamine. Which of the following is MOST likely implicated in her seizures? a. Toxic metabolite of atracurium b. Digoxin toxicity c. Accumulation of fentanyl metabolites d. Meperidine e. Meropenem

4. Atracurium Non-depolarizing neuromuscular blocking agent, first synthesized in 1974 Cisatracurium = purified R-cis R-cis isomer Metabolization of Paralytics: Succinylcholine, Mivacurium  Cholinesterases Vecuronium  Deacetylated and excreted in bile Atracurium  Hoffman degradation Side effects: Renal failure can lead to increased laudanosine

5. Digoxin Purified glycoside similar to Digitoxin (isolated from the foxglove plant) First described by William Withering in 1785 Mechanism: Binds to myocardial Na-K-ATPase pump Increases intracellular Ca+ Longer Phase 4 and 0 Adverse effects: “PAT with Block” Seizures ~ 0.1%

6. Fentanyl Synthetic opioid first synthesized by Janssen Pharmaceuticals in 1959 Mechanism of actions: Bind mu-receptors to inhibit neurotransmitter release in pain fibers High lipophilicity allows for easy CNS penetration Clearance: Primarily cleared by the liver No active metabolites

7. Meperidine Also known as… Demerol! First synthetic opioid (1932) Acts primarily at mu recep May act at the kappa-receptor to stop shivering Clearance: Metabolized to normeperidine Normeperidine is cleared in the urine Elevated normeperidine levels are associated with seizures (often fatal)

8. Meropenem Carbapenam antibiotic Similar class: Imipenem, Ertapenam Mechanism: Beta-lactam  inhibits bacterial cell-wall synthesis Resistant to beta-lactamase Adverse Effects: Most common = diarrhea, nausea, vomiting C.diff in 3.6% of patients taking Meropenem

9. You’ve got the shakes… A 6-year-old with renal failure develops seizures after 6 days in the PICD. Her medications include fentanyl, meperidine, digoxin, atracurium, meropenem, and dobutamine. Which of the following is MOST likely implicated in her seizures? a. Toxic metabolite of atracurium b. Digoxin toxicity c. Accumulation of fentanyl metabolites d. Meperidine e. Meropenem

10. My heart is racing! A 14-year-old male quadriplegic is postoperative day 7 following spinal surgery to stabilize a C4-5 fracture. He had been doing well for several days. You are called to his bedside emergently for acute tachycardia (HR 175) and hypertension (BP 220/130). He is awake and diaphoretic. You note that he has been oIiguric for over 10 hours. The best initial response in this scenario is to: a. Obtain blood cultures and start broad spectrum antibiotics· b. Obtain an emergent head CT scan c. Institute beta blocker therapy d. Catheterize the bladder e. Administer intravenous fluids until urine output is established

11. Bladder Innervation

12. Bladder Function with SCI Throaco-lumbar Injury (Sympathetic) Decreased internal sphincter tone Decreased distensibility of the bladder Sacral Injury (Parasympathetic) Increased internal sphincter tone Increased bladder distension Rostral Spine Injury (Somatic) Stretch receptors and spinal reflexes intact, but loss of EUS control Frequently develop spasms as the bladder contracts against a closed EUS

13. My heart is racing! A 14-year-old male quadriplegic is postoperative day 7 following spinal surgery to stabilize a C4-5 fracture. He had been doing well for several days. You are called to his bedside emergently for acute tachycardia (HR 175) and hypertension (BP 220/130). He is awake and diaphoretic. You note that he has been oIiguric for over 10 hours. The best initial response in this scenario is to: a. Obtain blood cultures and start broad spectrum antibiotics· b. Obtain an emergent head CT scan c. Institute beta blocker therapy d. Catheterize the bladder e. Administer intravenous fluids until urine output is established

14. Speaking of hearts… A 4-year-old girl status post complete repair of Tetralogy of Fallot develops tachycardia on the first postoperative night. Her surface ECG (bottom) and simultaneous univentricular atrial wire recording (top) are shown in the figure below. Based on the electrocardiograms the most likely diagnosis of her tachycardia is: a. Atrial fibrillation b. Atrial flutter c. Junctional ectopic tachycardia d. Ectopic atrial tachycardia e. Sinus tachycardia

16. Atrial Fibrillation Automatic signals from multiple foci in the atrium, often around the pulmonary veins Result in atrial “quivering”, but near-normal ventricular conduction

17. Atrial Flutter Rapid atrial contractions due to a re-entrant circuit (usually in the RA in infants) Rare in infancy, this condition usually resolves after conversion Characteristic saw-tooth patterns in II, III, and aVF

18. Ectopic Atrial Tachycardia Impulse arises from a single ectopic focus in the atrium Accounts for 10-20% of all pediatric SVT

19. Back to the question at hand…

20. Junctional Ectopic Tachycardia Enhanced automaticity in the region of the AV-Node Features: AV Dissociation Ventricular rate > Atrial rate Usually occurs in the immediate post-op period Causes: May be inflammation/injury of conducting fibers Family history in 50-55% of adult patients Most common occurrence is after Tet Repair

21. Take a deep breath… Which of the following findings in a tracheal aspirate is MOST indicative of bacterial pneumonia in a patient who has been ventilated in your PICU for one week? a. 15,000 colony-forming units of Gram-negative rods on a bronchoalveolar lavage b. Gram-positive organisms in chains on a gram stain of tracheal aspirate c. Positive tracheal aspirate for Pseudomonas d. Lobar infiltrate that clears within 24 hours e. Positive blood culture for coagulase-negative staphylococci

22. Make a match… Na+Cl-K+CO2 1561103.522 130904.022 148932.828 130924.515 Match the disease entity with the most likely set of serum electrolytes: a) Diabetes insipidus b) Syndrome of inappropriate antidiuretic hormone secretion c) Diabetes insipidus d) Hyperaldosteronism

23. Our friend the nephron

24. Diabetic Ketoacidosis Anion-Gap Acidosis and Hyperglycemia Low insulin  inability to utilize glucose Production of beta-hydroxybutyrate, acetoacetic acid Potassium Extracellular shifts due to acidosis, lack of insulin Wasted in urine (H-K-ATPase symporter) Sodium Pseudohyponatremia due to hyperglycemia “True Na” = (Measured Na) + 1.6x[(Glucose -100)/100]

25. Diabetes Insipidus Central DI: Lack of ADH production from the posterior pituitary Nephrogenic DI: Inability of the collecting duct to respond to ADH V2 Receptor located on X-q28 Aquaporin-2 Receptor accounts for ~10% of congenital cases Loss of ADH: Inability to resorb free H2O  excessive, dilute UOP Hypovolemia  increased aldosterone

26. SIADH Release of excessive ADH Associated with CNS pathology (tumor, TBI, etc.) Can be induced by carbamazepine, cyclophosphamide Results: Retention of H2O  volume expansion Depressed aldosterone

27. Hyperaldosteronism Aldosterone Primary mineralocorticoid Synthesized in zona glomerulosa Normal actions: Distal convoluted tubule  K+ and H+ excretion Collecting duct  Na+ and Cl- resaborption H2O follows Na+ Excessive states: Metabolic alkalosis and hypokalemia

28. Make a match… Na+Cl-K+CO2 1561103.522 130904.022 148932.828 130924.515 Match the disease entity with the most likely set of serum electrolytes: a) Diabetic ketoacidosis b) Syndrome of inappropriate antidiuretic hormone secretion c) Diabetes insipidus d) Hyperaldosteronism

29. References Rogers’ Textbook of Pediatric Intensive Care, 4 th Edition Livingstone, “Pharmacology of Muscle Relaxants and their Antagonists” 2000 Dean M. “Opioids in renal failure and dailysis” Journal of Pain and Symptom Management, 2004 Labroo RB, et.al. “Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implications for interindividual variability in disposition, efficacy, and drug interactions” Drug Metabolism and Disposition 1994 Arnold R., Verrico P., and Davison SN, “Opioid use in renal failure”, Medical College of Wisconsin, 2009 Thulhammer F. and Horl WH, “Pharmacokinetics of meropenem in patients with renal failure and patients receiving renal replacement therapy” Clinical Pharmacokinetics 2000 Yoshimura N, “Bladder afferent pathway and spinal cord injury: possible mechanisms inducing hyperreflexia of the urinary bladder”, Progress in Neurobiology 1999 “Guidelines for Diagnosis and Reporting of Ventilator Associated Pneumonia” CDC.gov, 2013 Fagon J, et.al. “Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia.” Annals of Internal Medicine, 2000 Chastre J, et.al. “Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia.” American Journal of Respiratory and Critical Care Medicine, 1995 Imamura M, et.al. “Prophylactic amiodarone reduces junctional ectopic tachycardia after tetralogy of Fallot repair”. Journal of Thoracic and Cardiovascular Surgery.2011 UpToDate.com (multiple topics) Emedicine.com (multiple topics)