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January 2014
Stanford University
Loren D. Sacks, MD
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
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
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
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%
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
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)
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
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
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
Bladder Innervation
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
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
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
Atrial Fibrillation
 Automatic signals from multiple foci in the atrium,
often around the pulmonary veins
 Result in atrial “quivering”, but near-normal
ventricular conduction
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
Ectopic Atrial Tachycardia
 Impulse arises from a single ectopic focus in the
atrium
 Accounts for 10-20% of all pediatric SVT
Back to the question at hand…
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
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
Make a match…
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
Na+
Cl-
K+
CO2
156
110
3.5
22
130
90
4.0
22
148
93
2.8
28
130
92
4.5
15
Our friend the nephron
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]
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
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
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
Make a match…
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
Na+
Cl-
K+
CO2
156
110
3.5
22
130
90
4.0
22
148
93
2.8
28
130
92
4.5
15
References
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Rogers’ Textbook of Pediatric Intensive Care, 4th 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)