key: cord-0036551-iy591hqk
authors: nan
title: Ethics
date: 2006
journal: Pediatric Critical Care Review
DOI: 10.1007/978-1-59745-105-5_15
sha: 361ecad85f2bbb23a75180ee5636b71b5b3e985d
doc_id: 36551
cord_uid: iy591hqk

The following chapter will focus on ethics. Pertinent questions, answers, and rationale will be reviewed. Answers for this chapter can be found beginning on page 162.

2. Children who can make their own decisions and give consents for medical treatment separate from their parents include: a. Children who are pregnant or are already parents. b. Children who graduated from high school. c. Children who have joined the armed forces. d. Children who live separately and independent from their parents. e. All of the above. 3 . Appropriate statements pertaining to the mature minor doctrine include all of the following except: a. A minor (child) should have the opportunity to accept or decline life-sustaining treatment, such as mechanical ventilation or dialysis. b. The child may refuse a blood transfusion that might otherwise be essential for appropriate medical care, if this is because of long-standing, well-thought beliefs, such as those held by adolescents who are Jehovah's witnesses. c. The law does recognize that some children have legitimate independent claims regarding their medical care that may differ from the expressed wishes of their parents. d. This legal entitlement means that the proposed decision maker is actually competent. e. Physicians must assess the decision-making capacity of patients or their surrogates. 4 . In order to give an informed consent, the patient or legal guardian must possess a decision-making capacity. This capacity has several features and elements that include all of the following except: a. The patient or surrogate does not need to have the ability to manipulate the information provided to them. b. Capacity includes the ability to deliberate about alternative options. c. Capacity to make medical decisions involves specific determinations for each significant decision. d. Capacity involves the ability to understand and communicate about the medical situation. e. Capacity involves the ability to make a choice among alternatives. 5 . You are involved in the treatment of a critically ill child with sepsis and multiple organ dysfunction syndrome at a university children's hospital. In this situation, all of the following actions and statements are true except: a. Parental religious beliefs should not prevent this child from receiving a clearly beneficial therapy. b. The best interest of the child should remain the guiding principle in most cases where there is any dispute with the parents. c. Treatment can go forward with permission from only one parent. d. When parents refuse involvement of trainees in the care of their child, the best course of action is to remind them that this is a teaching institution and proceed with the care with your trainees. e. Children may receive treatment by court approval over and against parental wishes, when the therapy constitutes the standard of care. 6 . In order for a patient to succeed in a claim for damages, he/she must prove: a. That the physician failed to meet the standard of care. b. That the physician's error led to legally recognized injuries. c. That the physician's error approximately caused the patient to suffer legally recognizable damage. d. All of the above. e. A only.

7. Regarding the doctor-patient relationship involved in a malpractice suit, which of the following statements is true? a. It is illegal to alter patient's medical records at a later time even when a reason for an addition is indicated. b. It can be hard to deny charges that inappropriate care was provided when the medical record has little or no information. c. When a physician treats a patient with a chronic medical problem, he/she is liable for the entire problem even after one encounter. d. Most jurisdictions state that the physician is responsible for the patient's noncompliance. e. All of the above. 8 . In the United States, a 14-year-old who is healthy without any significant past medical history is most likely to die from: a. Suicide. d. Accident. b. Homicide.

e. Brain tumor. c. Leukemia. 9 . "Baby Doe" regulations include that health care providers cannot withhold medically beneficial treatment from a child on the basis of a handicap. An exceptions includes: a. If the infant is imminently dying. b. The treatment would be inhumane. c. The infant is permanently comatose. d. All of the above. e. A and B only.

10. You are called to the pediatric intensive care unit (PICU) as soon as possible because the parents of a 6-month-old child with Down's syndrome and atrioventricular canal defect in congestive heart failure are very angry at the staff, and are expressing dissatisfaction with the care provided to their child. Upon your arrival, you notice the father is indeed very angry and is asking to transfer his child to another institution. All of the following would be appropriate responses except: a. Listening to their concerns is one of the most effective interventions in dealing with this family. b. A team meeting with this family should be promptly convened. c. You should remind the parents that you and the staff were up all night taking care of this child, and at this point, everybody on the team is somewhat tired and exhausted. d. Accept the emotional outburst of the father calmly. e. Assure the parents that their child is being appropriately cared for and comforted.

11. Measures that can be taken to prevent hostility among parents, such as the ones in Question 10, include: a. Orientation to policies of the PICU as soon as possible after the admission of the child. b. Introduction of the staff soon after admission. c. If there is evidence that the parents are showing signs of dissatisfaction with the care, a team meeting with the family should be promptly convened. d. Family education to alleviate any knowledge deficit. e. All of the above. 12. A 12-month-old baby of a single mother, who was apparently being watched by the mother's boyfriend, was admitted to your PICU for persistent seizures. Physical examination was significant for the presence of multiple retinal hemorrhages, and the computed tomography scan revealed intracerebral hemorrhage and a subdural hematoma. Correct statements pertaining to this case include all of the following except: a. A complete copy of the medical record is extremely helpful during the initial investigation. b. If you are asked to testify in court regarding this case, a monitory compensation is expected. c. Accidental injury, other than a car accident, rarely causes intracranial injury in infants. d. Remind your staff that the parents of this child should be treated in the same professional and supportive manner that is employed with the parents of any other critically injured child. e. In discussing this case with one of your residents who will be testifying in court, it is crucial to remember that most physicians are unprepared by training and experience to go to court as expert witnesses.

The same principles applied for tracheal intubation in a patient with closed head injury should be applied here. ( 15. C In a patient with closed head injury, one should avoid ketamine because it increases intracranial pressure, possibly through a cholinergic mechanism. In a setting of hypotension and shock, thiopental, particularly in the usual dose of 2-4 mg, should be avoided because it may potentiate hypotension, which might be detrimental to the patient. Vecuronium seems to cause minimal hemodynamic disturbances, and therefore, in combination with lidocaine and low-dose (1-2 mg/kg) thiopental would be the most appropriate combination in this patient. ( 

A In a patient with hypovolemia or shock, ketamine seems to be the most appropriate choice because it is a cardiovascular system stimulant, along with vecuronium, which is associated with minimal hemodynamic disturbances would be most the most appropriate combination. 17. D With turbulent airflow, the resistance to airflow is proportionate to density. A helium-O 2 (HeliOx) mixture has a lower density than an O 2 -nitrogen mixture. This leads to a reduced resistance to airflow. Use of an oxyhood is not recommended because helium tends to separate as a layer at the top of the oxyhood. It usually is given through a tight-fitting face mask. The ventilator transducer is calibrated with an air-O 2 mixture, and therefore, with a HeliOx mixture, the tidal volume may not be accurate unless it is measured directly. (Kemper KJ. Crit Care Med, 1991; 19:356; Ellean C. J Pediatrics, 1993; 122:132-135.)

18. E The theory is that increased negative interstitial pressure is a contributing factor to the development of pulmonary edema in association with upper airway obstruction. To further review theories that explain the development of pulmonary edema in children with croup and epiglottitis, see the following ref- 19,20. E, E Children who develop hyaline membrane disease or have pulmonary hypoplasia owing to a wide variety of reasons including diaphragmatic hernia, children with tracheoesophageal fistula, and those who develop early neonatal infections resulting from, but not limited to, group B streptococcal infection, ureaplasma, respiratory syncytial virus, or cytomegalovirus, seem to be at a higher risk of developing bronchopulmonary dysplasia. Other risk factors include male sex, white race, and a birth-weight of less than 750 g. (Kennedy KA. Semin Perinatol, 1993; 17:247.) 21. D Negative, rather than positive, pleural pressure has a tendency to promote formation of pulmonary edema. All other factors in the question tend to promote pulmonary edema. (Robin ED. N Engl J Med, 1973; 288:239.)

23-24. E, D Air within the connective tissue sheath leads to compression of the surrounding peripheral airway with subsequent increased airway resistance and hyperinflation. Impaired lymphatic drainage promotes pulmonary edema. Once extra-alveolar air develops, it may dissect into the subcutaneous space and mediastinum. Further extension into the pericardium and peritoneum may occur. The primary event appears to be epithelial necrosis. 25. D Infants with bronchopulmonary dysplasia (BPD) have been shown to have a blunted arousal response to hypoxia. Increased chest wall compliance places these infants at a mechanical disadvantage, particularly during periods of decreased or low intercostal muscle activity, such as during rapid eye movement during sleep. The peripheral chemoreceptors are intact in these babies. Prolonged ventilatory support may lead to disuse atrophy of respiratory muscles. 26. E Normally, the blood flow through the right coronary artery occurs during both diastole and systole, as opposed to the blood flow through the left coronary artery, which occurs primarily during diastole. In infants with bronchopulmonary dysplasia, with the development of pulmonary hypertension and particularly with progressive pulmonary hypertension, the blood flow through the right coronary artery becomes limited to diastole as right ventricular pressure and volume increase. (Berman W. Pediatrics, 1982; 70:708.) lung volume. This would lead to an increase in functional residual capacity (FRC). It is decreased during active sleep because it is arousal-dependent. Specific compliance and specific conductance are the same for adults and children. (Kosch PC, Stark AR.J Appl Physiol, 1984; 57:1126 -1133 48. B Time constant = resistance × compliance. Whenever one of the components of the time constant (i.e., either the resistance or the compliance) increases, the movement of air from one lung unit to another would be prolonged, leading to an increase in the time constant. Therefore, applying these principles in the diagram, because the resistance in the airway leading to unit A is increased, and the compliance of unit C is also increased, these two units will contain less volume of gas when inflation is interrupted prematurely. 60. B Peripheral chemoreceptors respond to a falling oxygen saturation in a linear fashion by increasing the inspired minute ventilation. There is an exponential increase in minute ventilation as PaO 2 falls, particularly at PaO 2 less than 60 torr. (Berger AJ, et al. N Engl J Med, 1977; 297:194-198.) 61. D Laryngeal and bronchial receptors respond to increasing CO 2 in a linear fashion. (Berger AJ, et al. N Engl J Med, 1977; 297:194-198.) 62. D The carbon dioxide response curve which relates alveolar CO 2 to alveolar ventilation is shifted to the left in the neonate. (Rigatto H. Apnea. Pediatr Clin North Am, 1982; 29:1105.) 63. D Preterm infants have a characteristic breathing pattern referred to as periodic breathing (i.e., pauses in respirations lasting 5-10 seconds). Owing to the higher O 2 demand, newborn infants compensate by having a higher minute ventilation and a shift in the CO 2 response curve to the left. The carotid bodies are present in preterm infants. (Rigatto H. Pediatr Clin North Am, 1982; 29:1105.) 64. D Total respiratory system compliance equals lung compliance plus chest wall compliance. With age, there is a progressive reduction in chest wall compliance which accounts for a reduction in the total respiratory system compliance. 70. B Babies who were born prematurely continue to be at high risk of apnea postoperatively (following general anesthesia) and therefore, should be monitored for 24-48 hours after anesthesia. Aminophylline will increase breathing without significantly altering the CO 2 and pH around the respiratory center. It appears to increase the sensitivity of the respiratory center to carbon dioxide. Patients with adenotonsillar hypertrophy who undergo surgical resection may be admitted to the pediatric intensive care unit (ICU) because of airway obstruction from postoperative edema or sometimes owing to decreased ventilatory drive after anesthesia. The increased opioid activity found in the spinal fluid in these patients may be a contributing factor to decreased ventilatory drive noted perioperatively. ( 

Dynamic compliance is smaller than static compliance because dynamic compliance is equal to the change in volume divided by peak inspiratory pressure minus positive end expiratory pressure (PEEP), as opposed static compliance, which equals volume divided by plateau pressure minus PEEP. Because peak inspiratory pressure is greater than the plateau pressure, the dynamic compliance would be smaller than the static compliance. 

Pulmonary edema is more likely to lead to a decrease in functional residual capacity rather than an increase in closing capacity. Elimination of secretions and use of effective bronchodilators are useful strategies to improve closing capacity.

A Because blood flow falls more dramatically than ventilation from the base of the lung toward the apex of the lung, the ventilation perfusion ratio increases exponentially as one moves up the lung. 113. D With an increase in met-Hb concentration, the saturation on the pulse oximeter decreases and plateaus at approximately 85%. Met-Hb absorbs light significantly at both 660 nm and 940 nm wavelengths, thereby confusing the pulse oximeter photo detector into believing that both oxy-Hb and reduced Hb are increased. This results in increases in both the denominator and numerator. As this happens, the microprocessor-driven algorithm of the red absorbance and infrared absorbance approaches unity and this gives rise to a saturation of approximately 85% on the calibration curve. 

The presence of a gas bubble in a syringe will usually affect the PaO 2 . The effect on the PaO 2 will depend on the amount of oxygen that is inspired by the patient. In patients on room air, this will lead to a false elevation of PaO 2 (atmospheric PO 2 is usually higher than alveolar PO 2 ). On the other hand, in patients who are receiving a high fraction of inspired oxygen and have normal lungs, the presence of an air bubble in a syringe may spuriously lower the PaO 2 . Excess heparin does lead to a drop in PaCO 2, but usually there are no changes in the pH level because it is neutralized by the acidity of heparin. ( 127. B π R 2 = 16 π when the diameter is 8 mm which gives rise to a radius of 4 mm. With a uniform 1 mm reduction in the size of the airway, this will decrease the diameter from 8 to 6 mm, and decrease the radius from 4 to 3 mm. Now π R 2 = 9 π, 9 ÷ 16 = 54%, which means that the diameter of the airway has been decreased by 44%. ( 

Maximum mid-expiratory flow rate is one of the flow volume parameters that demonstrates the most severe decrease during an attack of asthma. This is also the parameter that is the last to improve following treatment for acute asthma. Patients with asthma, particularly those that are in status asthmaticus, have an increased residual volume. 152, 153. D, D Transmural pressure = intraluminal pressure -extraluminal pressure. With higher negative inspiratory pressure, as seen with status asthmaticus, there is an increase in afterload during inspiration with a subsequent decrease in left ventricular output, which is followed by a sharp increase in left ventricular output during subsequent expiration. This leads to the phenomenon of pulsus paradoxus (PP). A decrease in PP may indicate an improvement in the patient's condition (i.e., a smaller fall in pleural), but it may also indicate the patient's fatigue and worsening clinical condition. Another factor that contributes to PP is ventricular interdependence, which can be exaggerated by the pulmonary hypertension, as it may be seen with severe status asthmaticus. The hypoxia that is seen during status asthmaticus results from V/Q mismatch, excessive O 2 requirement secondary to increased metabolic demand, and a degree of interstitial edema. ( The lungs emerge as a bud from the pharynx at day 26 following conception. This bud elongates, separates from the esophagus, and continues to divide to form the main bronchi. Extensive subdivision in the pseudoglandular stage leads to formation of the conducting airway, the most peripheral of which are the terminal bronchioles, which give rise to respiratory bronchioles and alveolar ducts during the canalicular stage. During this later stage, the acinus is formed. An acinus is the gas exchange unit associated with a single-terminal bronchiole, and will eventually contain three orders of respiratory bronchioles: alveolar ducts, alveolar sacs, and alveoli.

The Saccular stage was formerly thought to be the last stage of lung development prior to birth. However, because alveoli form before birth, the termination of this period is now arbitrarily set at 35-36 weeks' gesta-tion. At the beginning of this phase (28 weeks' gestation) the terminal structures are call saccules. They are cylindrical structures with a smooth wall. They become subdivided by ridges called secondary crests. Further subdivision between crests results in small spaces termed subsaccules. Exactly when these subsaccules can be termed alveoli is a matter of debate. The range of timing is between 29-36 weeks' gestation. Most of postnatal formation of alveoli occurs over the first 1-1. 5 

The Mapleson D breathing circuit (shown in figure below) can be described as a T-piece with an expiratory limb. The fresh gas inlet is located near the patient, and the expiratory pressure release valve is near the reservoir bag. The pressure release valve opens as pressure increases during expiration and a portion of the expired gas along with fresh gas is released into the atmosphere. During the next inspiration, the patient receives a combination of fresh gas and the exhaled gas. The content of this inspired gas is determined by:

1. Rate of fresh gas flow: A fresh gas flow more than two times the minute ventilation prevents rebreathing. 2. Patient's tidal volume: the amount of rebreathing increases as the tidal volume increases. 3. Duration of expiration: a short expiratory pause provides inadequate time to flush the alveolar gas (occurs with faster respiratory rate); this allows rebreathing.

(Barash PG, Cullen BF, Stoelting RK. Clinical Anesthesia, 2nd Edition; pp. 654.)

173. C When peak airway pressure is allowed to increase to a level beyond that which is necessary to maximally distend the lungs, barotrauma and lung injury result. Because regional differences in lung resistance and compliance often coexist, maintaining a constant tidal volume may overdistend areas of the lung that are aerated if the remainder of the lung is collapsed. Similarly, maintaining a constant inspiratory flow pattern when regional differences in lung units exist will selectively increase distention of lung units with lower resistance. (Haake R, et al. Chest, 1987; 1:608.) 174. D Pulmonary conditions associated with decreased compliance, such as pulmonary fibrosis and ARDS or increased airway resistance such as bronchial asthma and chronic obstructive pulmonary disease (COPD), have the potential for being homogenous. This homogeneity can result in regional overdistention during positive pressure ventilation. Hyperinflation secondary to airway narrowing or collapse, such as seen with auto-PEEP, increases end-expiratory lung volume, but does not result in lung expansion of the hyperinflated lung units until airway pressure exceeds the level of auto-PEEP. Although the work of breathing during spontaneous breathing is increased by auto-PEEP, end-inspiratory lung volumes do not increase. (Bone RC, Stober G. Med Clin Noth Am, 1983; 67:599.) 175. D Changes in intrathoracic pressure correlate highly with changes in lung volume. Changes in intrathoracic pressure are independent of lung compliance. An increase in respiratory rate with lung conditions associated with increased expiratory airway resistance will result in dynamic hyperinflation, because there is inadequate time for exhalation. Examples are COPD, asthma, and other causes of intrathoracic airway obstruction. Thus, overdistention is possible with a fixed tidal breath or tidal volume. Because regional lung compliance, even in healthy individuals, is different under all conditions, uniform expansion of all lung units by positive pressure ventilation at any setting probably never occurs. ( 178. D Systemic-to-pulmonary shunt is often created in neonates and infants with an underlying cardiac defect in order to improve pulmonary blood flow and oxygenation. Examples are the (modified) Blalock-Taussig shunt that connects the subclavian artery to the pulmonary artery using a synthetic material, and the aortic to pulmonary window, which usually connects the ascending aorta to the pulmonary artery. Conditions that lead to a reduction in pulmonary artery pressure and pulmonary vascular resistance would increase the flow across the shunt with an increase in left-to-right shunt. Examples include: alkalosis, vasodilators such as hydralazine and nitroprusside, an increase in the concentration of inspired oxygen, and selective pulmonary vasodilators, such as nitric oxide. Interventions that lead to an increase in pulmonary vascular resistance, such as increasing PEEP, would lead to a reduction in pulmonary blood flow and a reduction in the left-to-right shunt. 182. C Histological features of infants with BPD include squamous metaplasia of the airway epithelium (large and small airways), increased peribronchial smooth muscle with fibrosis, submucosal edema, and inflammation with hypertrophy of submucosal glands. In the parenchyma, there are areas of fibrosis with atelectasis alternating with areas of hyperinflation, which, on gross examination of the lungs, has a cobblestone appearance. In more long-standing cases, there is diminution in alveolarization and surface area. The decrease in the number of alveoli probably reflects the onset of the insult with subsequent failure of the ability to regenerate new alveoli. This is associated with an increased number of small pulmonary arteries, which may contribute to pulmonary hypertension. The pulmonary arterial tree shows proliferation of the intima, smooth muscle hypertrophy, distal extension of smooth muscles, and adventitial thickening. 186. E Hysteresis refers to the failure of a system to follow identical paths of response during application and during withdrawal of a force. In the lungs, this is due mainly to surface properties and alveolar recruitment-derecruitment. In the chest wall, this is because of muscles and ligaments, both of which exhibit hysteresis. (Taussig LM. Pediatric Respiratory Medicine, 1999; pp. 100-101.)

A Increasing the length of muscle fibers (to a limited extent) would increase the force of contraction and thus the efficiency of the diaphragm. The diaphragm is most efficient at the lung volume that corresponds to the FRC, and thus increasing the end-expiratory lung volume above this does not improve the efficiency of the diaphragm. Increasing the radius of curvature increases the efficiency of the diaphragm. The diaphragm of an infant has less radius of curvature than that of an adult, and is less efficient. ( In order to keep the PaO2 the same, and therefore compensate for the same degree of alveolar-arterial oxygen gradient as the atmospheric pressure decreases, the alveolar oxygen tension must remain the same (i.e., 192.51). Therefore, 195. E Type I alveolar cells are less in number than type II alveolar cells (which synthesize surfactant), but they cover a much larger area of the lung. Their primary function is to reduce the barrier to gas exchange. ( 10, 11. D, D Myocardial wall tension is directly proportional to intraventricular pressure and also directly proportional to the intraventricular volume. However, myocardial wall tension is inversely proportional to the myocardial wall thickness. Therefore, in a situation where the wall of the myocardium is thin, there is an increase in myocardial wall tension, and this is likely to lead to increased myocardial oxygen consumption because the majority of oxygen consumed by the heart is utilized by myocardial wall tension. A heart that is dilated (which means that there is increased intraventricular volume associated with a large preload) in the presence of a thin left ventricular wall is a heart that would be considered least efficient. ( 29. D Cyanosis in the face of a normal PaO 2 occurs with smoke inhalation, which is particularly associated with CO poisoning. An overdose on shoe dye leads to met-hemoglobinemia. Both these clinical conditions are characterized by a normal arterial oxygen tension, but a decreased measured oxygen saturation. Patients with a very high hematocrit also may present with cyanosis, which is usually a peripheral cyanosis in the presence of a normal PaO 2 . ( 33. C These findings suggest that there is increased pulmonary blood flow, which is likely to lead to pulmonary congestion, and also a diastolic overload on the right ventricle. Use of hyperventilation and tolazoline will lead to further pulmonary congestion and may lead to deterioration of the patient's overall condition. (Nichols DG, et al. Critical Heart Disease in Infants and Children, Mosby, 1995; pp. 863-868.)

following an extrapericardial procedure, usually a pal-liative procedure such as a systemic-to-pulmonary shunt. Prior to enteral feeding, the pleural fluid may be serosanguinous. It turns into a milky color following enteral feeding. Malnutrition because of loss of protein and fat is a recognized complication, which must be managed appropriately. All are indications for surgical ligation of the thoracic duct for persistent cholothorax. 

The purpose of the modified Fontan procedure is to eliminate the obligatory diastolic overload on the single ventricle and also to improve oxygenation. Following the Norwood procedure, a systemic-to-pulmonary shunt is created, and any situation that increases pulmonary vascular resistance leads to a decreased pulmonary blood flow, with subsequent hypoxemia. On the other hand, an increase in pulmonary vascular resistance in a patient with a modified Fontan procedure will lead to cardiogenic shock. This is owing to the fact that blood flow from the right side of the heart to the lungs is gravity-dependent because of absence of a contractile right heart. (Nichols DG, et al. Critical Heart Disease in Infants and Children, Mosby, 1995; pp. 868-874.)

The creation of a fenestration between the upper chambers of the heart will allow shunting of the blood from the right side to the left side of the heart in a setting of increased pulmonary vascular resistance, which in turn will maintain cardiac output. It has also been shown to decrease incidence of pleural effusion and mortality. The fenestration can be closed in a cardiac catheterization laboratory at a later date. 

Nitroglycerin tends to decrease central venous pressure and pulmonary artery occlusion pressure without significantly lowering blood pressure. Therefore, it is the preferred drug in patients with marginal blood pressure. Sodium nitroprusside, on the other hand, is the preferred drug for patients who have a preserved blood pressure. Shock is the major contributor to mortality in these cases. Cases of hypovolemic shock can be successfully treated with crystalloid solutions when sufficient volumes are administered. It has been shown that replacement of up to 50% of the total blood volume of the patient with crystalloids is not associated with significant expansion of the interstitial space. Fluid administration equivalent to 200% of blood volume will result in edema fluid accumulation, particularly if administered rapidly. Hetastarch is available as 6% solution in 0.9 saline. Therapeutically it is equivalent to albumin but the cost is much less. The administration should not exceed 10-20 mL/kg/day because of the concern about derangement in hemostasis. Carcillo et al. (JAMA 1991) found that fluid resuscitation rapidly in excess of 40 mL/kg in the first hour was associated with improved survival in children with septic shock. The risk of pulmonary edema was not increased. Plasma catecholamines are significantly elevated in shock states and impaired cellular metabolism occurs early with septic shock. 

Various portals of entry of the organism into the body are recognized. In 20% of cases, a portal of entry is not found based on history and physical examination, and therefore, absence of the portal of entry is not very rare. Also of note, is that cultures may not reveal the causative organism. Generalized seizures are not a recognized feature of tetanus; however, the so-called "respiratory convulsions" can develop and require immediate attention to opening and maintaining the airway, which often includes endotracheal intubation. The mortality resulting from tetanus is most commonly secondary to respiratory abnormalities. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp. 241-244.)

Autonomic dysfunction is a recognized feature of both poliomyelitis and Guillain-Barre syndrome, and the mortality in both results from respiratory dysfunction. Poliomyelitis generally presents with asymmetric scattered weakness, as opposed to the symmetric weakness that is noted with Guillain-Barré syndrome, and the clinical progression is usually rapid with poliomyelitis. ( 

Diaphragmatic paralysis secondary to a phrenic nerve injury most commonly follows a palliative repair of a congenital cardiac defect such as a Blalock-Taussig shunt. In infants and children, this entity is much more likely to lead to gas exchange abnormalities and could be analogous to a flail chest in an adult. This arises because of the highly compliant chest wall and poor ability of the intercostal muscle to stabilize the chest wall. Congenital myasthenia gravis has an onset a few days after birth with poor feeding and respiratory difficulty/failure. Family history is often present in a sibling, but history of myasthenia in the mother during pregnancy is absent.

Neonatal myasthenia gravis is uniformly born to mothers with myasthenia gravis; one out of five is transient in nature (as the autoantibodies resolve), and responds well to anticholinesterase medications.

Familial infantile myasthenia gravis is usually not born to mothers with myasthenia gravis even though there is often history of myasthenia gravis in a sibling. These patients develop marked respiratory depression and require tracheal intubation. The subsequent clinical course is characterized by episodes of muscle weakness in the first 2 years of life, which may progress to respiratory failure. Episodes do respond to anticholinesterase therapy.

Following general anesthesia with tracheal intubation, patients with myasthenia gravis may develop stridor with or without respiratory distress secondary to the following factors: glottic/subglottic edema owing to traumatic intubation, laryngeal muscle weakness, or vocal cord paralysis. ( 45. D Diazepam is one of the most lipid-soluble of anticonvulsants, and therefore, it has a very large Vd because of its high lipid solubility. The Vd of diazepam is at least five times that of lorazepam, and diazepam has significant metabolites, which tend to accumulate and contribute to the prolonged or delayed effects. 58. E Cerebrospinal fluid rhinorrhea is seen in approximately 7% of basilar skull fractures, and the in the vast majority of cases it resolves within a period of a few weeks. Ecchymosis in the periorbital area is referred to as racoon's eye. Corticosteroids have not been shown to be definitely beneficial in a setting of closed head injury. Cerebrospinal fluid rhinorrhea is uncommon in children less than 10 years of age because of underdevelopment of sinuses. ( 

The prophylactic use of antibiotics does not significantly decrease the incidence of infection associated with intracranial pressure monitoring devices, and therefore, use of prophylactic antibiotics in this setting is not indicated. Increasing the frequency of breaks into the system, such as obtaining samples or flushing the catheter with saline, does increase the risk of infection. However, placement of these catheters either in the ICU or the operating room has not been shown to make a substantial difference in terms of the rate of infection. 

Early-onset neonatal group B streptococcal infections are usually seen within the first week of birth. Early-onset disease is primarily a disease of premature infants less than 35 weeks gestation and weighing less than 2500 g at birth. Late-onset infection can be delayed up to 3 months after birth. There is a poor correlation between the late-onset group B streptococcal infection and maternal colonization, 95% of the isolates are type III, and there is a higher association with meningitis, as opposed to association with pneumonia that is seen with early-onset group B streptococcal infection. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp. 1016,1017.) 11. T, F, T, T, F, T, T, T The initial antibiotic therapy of the sick neonate generally consists of ampicillin and an aminoglycoside. Whereas the combination of ampicillin and gentamicin is synergistic against group B streptococcal infection, the addition of chloramphenicol to ampicillin is of no additional benefit. The immaturity of the immunological system of the newborn predisposes this group of patients to susceptibility to group B streptococcal infection. It is the deficiency in complement, antibodies, and plasma components that is thought to be responsible for the short-term outcome improvement in simple and double volume exchange transfusions. Listeria monocytogenes generally affects extremes of age and pregnant women, and it has a bimodal presentation similar to group B streptococcal infection (i.e., early-onset and late-onset). 13. D The majority of infections in which a source is identified are related to maternal genital infections. The incubation period for neonatal herpes is usually longer than 7 days. The likelihood of the neonate contracting the disease is correlated with a prolonged rupture of membranes (>6 hours) in a mother with active genital infection. ( 16. D Several attempts at classifying meningococcal disease severity and prognosis have occurred. The characteristics that are associated with a worsened outcome represent failure of the child's organ systems to adequately compensate for the disease. A low leukocyte count in the periphery or in the cerebrospinal fluid (CSF) may represent a failure of the host's neutrophils to mount an adequate response. Similarly, the presence of shock, petechiae, and thrombocytopenia are unfavorable. The elevation of the sedimentation rate is, in part, owing to elevation of the acute phase reactants, which includes fibrinogen, and this will take at least 24 hours. A sedimentation rate of 100 mm/hour (as stated in the question) would suggest that the infection has been going on for more than several hours, and it would constitute a good prognostic feature. ( 17. D The cardiovascular collapse and instability associated with meningococcal infection was originally thought to be resulting primarily from adrenal dysfunction. However, large doses of exogenous corticosteroids were not always effective in reversing the shock state, and therefore, the more recent prevailing theory is that the cardiovascular collapse is actually secondary to endotoxemia, with its effect in inducing multiple organ dysfunction syndrome. Fulminant meningococcemia has an estimated mortality rate of 85%. Petechiae are frequently present in this disease and are related to a failure of the hematopoietic system and disseminated intravascular coagulation. Corticosteroids are a promising intervention that have not been demonstrated to universally reverse the shock state. ( 

A history of freshwater lake swimming is an important etiological risk factor for N. meningitis. Otitis media is often seen in association with H. influenzae meningitis. Meningitis in the vast majority of cases does not actually involve the parenchyma. It is limited to the three layers of the meninges. The Virchow-Robin spaces are a continuous extension of the subarachnoid space, which will allow the bacteria to gain access into the subarachnoid space, and maybe to the most superficial surface of the brain. Meningitis, when severe, is often associated with cerebral edema. 28. E By day 5 of treatment with antibiotics, 85% of children with H. influenzae meningitis will be afebrile. SIADH has been noted in more than 50% of patients with meningitis. Under these circumstances, restriction of fluid and close monitoring of fluids and electrolytes are a necessary part of the management of these patients. Subdural effusions, which are a recognized complication of meningitis, generally resolve spontaneously and do not require surgical intervention in the vast majority of cases. Nosocomial infection is a common cause of recurrent treatment after initial treatment for meningitis. 39. D Over the past 30 years, cyanotic congenital heart disease has replaced suppurative otitis media or mastoiditis and suppurative sinusitis as the most common predisposing factor for brain abscess. This is true for the industrial nation, but even in developing nations, it is the most likely predisposing factor. Overall, a predisposing factor can be determined in approximately 85% of all patients with brain abscess, and therefore, a meticulous evaluation for a predisposing factor is warranted in these patients. 41. D Normal brain parenchyma is highly resistant to invasion by microorganisms and therefore, abscess formation seems to occur only in areas of the brain with focal ischemia, necrosis, or marginal perfusion. Poor vascular supply in the white matter or at the junction of the gray and white matter makes these areas the most likely to be affected by brain abscess. With the exception of the neonatal period, abscess infrequently complicates a course of bacterial meningitis. In the neonatal period, Citrobacter diversus and Proteus mirabilis are the most common etiological agents that usually cause meningitis and are subsequently complicated by brain abscess. When seizures develop in association with brain abscess, they are most commonly a generalized seizure. In up to 30% of brain abscess cases, the microbiology is polymicrobial, which could be a combination of aerobic and anaerobic organisms. Suppurative complications of otitis media or sinusitis are becoming less and less common as an etiological agent or predisposing factors for brain abscess. Because of poor penetration into the abscess cavity, aminoglycosides are not effective for treatment of brain abscess. 42. D Unlike the epidural space, the subdural space is not limited by attachment of the dura to the skull sutures, allowing extension and the spread of the subdural empyema over a wide area of the cerebral hemispheres. The potential subdural space is restricted at the base of the brain, and therefore involvement of the base of the brain is rare with subdural abscesses. In infants, subdural empyema generally complicates acute meningitis, and therefore is caused by the organisms commonly implicated in causing meningitis. Because the incidence of H. influenza type B as a cause of meningitis in infants has decreased dramatically in the United States, this organism is becoming less and less an etiological agent for subdural empyema. The magnetic resonance imaging (MRI) is the diagnostic imaging procedure of choice for subdural empyema. Advantages of MRI over the computed tomography (CT) scan include the lack of bone artifact, the ability to detect the smaller extracranial fluid collection, and improved ability to differentiate extracranial collection of fluid from other differential diagnoses such as cerebritis, cerebral edema, and venous thrombosis. MRI can also detect the density difference from elevated protein concentration, and therefore distinguish a subdural abscess from other sterile collections, such as subdural effusions. 44. D Proposed and simplified diagnostic criteria for toxic shock syndrome in children include: fever equal to or greater than 39°C, lymphopenia, rash, shock, diarrhea and vomiting, and irritability. The Centers for Disease Control and Prevention has not adopted these simplified criteria, however. Toxic shock syndrome can also be caused by streptococci, and is one example of severe group A streptococcal disease. 

Rickettsia rickettsii. In the eastern regions of the United States, Dermacentor variabilis is the most common tick involved, whereas in the western region, the Dermacentor andersoni is the most common tic involved. The disease is usually prevalent in the summer months, and the highest incidence of disease among children age 5-9 years. More than half of all cases appear in persons younger than 19 years of age. The incubation period is 2-14 days, with an average of 7 days. Man is only incidentally involved when bitten by an adult tick. The initial presentation consists of headaches, malaise, and myalgias. The rash generally appears within 2-4 days after the fever, and has been noted in nearly all children with the disease. The eruptions begin as discrete macules, first observed on the ankles and feet, and shortly thereafter on the wrists and hands. Regardless of the pro-gression of the rash, the rash is almost always most pronounced over the extremities and almost always involves the palms of the hands and the soles of the feet. Over a period of several days, the rash becomes petechial and purpuric. ( 

The child with neoplastic disease may acquire a variety of neurological deficits related to the neoplasm, the therapy, or a combination of both. Methotrexate is associated with aseptic meningitis, arachnoiditis, demyelinization, somnolence, and chronic leukoencephalopathy. Cisplatin may cause ototoxicity, cerebral edema, and seizures. Vincristine is associated with SIADH. 5-FU may cause acute cerebellar ataxia. 

D Antithrombin III, protein C, and protein S are the main components of the antithrombotic system. Thrombomodulin and heparin cofactor II, among others, are also included as endogenous anticoagulants. Protein B is not included among these components. 15. E When the liver itself is diseased, abnormal coagulation results. The liver synthesizes fibrinogen, prothrombin, protein C, protein S, antithrombin III, plasminogen, and factors V, VII, IX, X, XI, and XII. 24. E Disorders in children that are treated with chronic anticoagulants include cardiac disorders (prosthetic valves, Blalock-Taussig shunts, endovascular shunts), some cerebrovascular events, and Kawasaki's disease. All of the above statements are correct. 

Kidneys are able to maintain renal blood flow over a wide range of systemic blood pressures by autoregulation of intrarenal vascular resistance. Therefore, hypotension with renal hypoperfusion may or may not produce ischemic renal injury. However, these autoregulatory mechanisms are not well developed in neonates. Neonates have high renin levels, which in turn, are associated with decreased glomerular filtration rate (GFR) and reduced outer cortical blood flow. The cortical glomeruli are immature and so are their corresponding tubules. This pattern of high renin and reduced outer cortical blood flow makes neonates more vulnerable to renal dysfunction as a result of hypotension of systemic pressures only slightly below the normal range. In animal studies, newborn animals have decreased production of atrial natriuretic peptide in response to saline challenge. All these factors combined make the incidence of acute renal failure in neonates, after cardiac surgery, higher than in older infants and children. (Nichols DG, et al. Critical Heart Disease in Infants and Children, Mosby 1995; pp. 125, 562.) 2. C Furosemide causes vasodilation of the cortical vasculature by direct action and through release of prostaglandins. Furosemide maintains renal blood flow and tubular blood flow when cardiac output is compromised. Mannitol is also a vasodilator of the cortical vasculature that increases renal blood flow either directly by drawing fluid from extravascular to intravascular space, thus increasing total plasma volume, or by increasing prostaglandin production. Increased plasma volume alone does not fully explain the effects of mannitol, because volume expansion with saline improves renal blood flow without improving GFR. The improvement in GFR seen with mannitol is associated with a decrease in afferent and efferent arteriolar resistance, which is probably mediated by prostaglandins. (2) third space volume loss; (3) bilateral ureteral obstruction; (4) cardiac failure; and (5) increased intra-abdominal pressure. In this patient, the latter is important to recognize (because it appears that intravascular volume has been expanded and cardiac output is normal) because prompt surgery to relieve increased intra-abdominal pressure is associated with rapid diuresis. The development of this problem is best avoided by direct measurement of intraabdominal pressure either via the esophageal route or per gastrostomy. Data indicate that the abdominal wall should not be closed if pressure exceeds 20 mmHg. In this case, it is best to employ a silo with delayed closure to allow time for the compliance of the abdominal wall to increase. 

In the absence of significant symptoms, hypocalcemia does not need to be aggressively treated. Aggressive treatment with calcium in the presence of hyperphosphatemia, and particularly when the product of calcium and phosphorus exceeds 60, increases the risk of calcium deposition in various tissues within the body. Acidosis raises the level of ionized calcium and thus mitigates against the occurrence of symptomatic hypocalcemia. Caution must be exercised in correcting acidosis abruptly, as a rapid decline in the level of ionized calcium may precipitate tetany. Dysequilibrium syndrome is not seen with peritoneal dialysis, as the process is very slow, as compared with hemodialysis, which is done over a few hours. Such a high dose of vitamin C is unnecessary in patients with renal failure. Patients with hemolytic uremic syndrome (HUS) seem to have a better outcome with early institution of dialysis. 20. C Atracurium undergoes spontaneous degradation referred to as Hofmann degradation; however, some authorities believe that ester hydrolysis is the major pathway for degradation of atracurium. ( 

Henle, chlorothiazide at the distal tubule, spironol actone at the cortical collecting duct, and mannitol is freely filtered by the glomerulus.

absence of clinical signs of dehydration, hyponatremia, and a low urinary sodium. In SIADH, the urine osmolality continues to be high in spite of low serum sodium and osmolality. Congenital adrenal hyperplasia is associated with hyperkalemia and acidosis. Three percent salt given at an initial dose of 4 mL/kg will increase serum sodium by approximately 3-4 mEq/L and will abort the seizure. 5. C It is not uncommon to have hyperglycemia in association with a head-injured child. Most likely, as a result of an increase in catecholamines and corticosteroids, there is an increase in blood sugar. Hyperglycemia has already been shown to be associated with the degree of severity in brain injury. Some data suggests that ischemic brain injury may be worse in those patients who have hyperglycemia in their recovery phase as opposed to those patients who had normoglycemia. Any coagulopathy that may exacerbate an ischemic picture also may worsen the severity of brain injury. 6. E The first step in the treatment of hypoglycemia in a child is initiation of dextrose bolus followed by an infusion of 10% dextrose. All of these conditions are characterized either by the inability to release glycogen from the liver or depletion of glycogen from the liver, and therefore, glucagon is unlikely to be effective. 7. E The stimulus for the mechanisms which elevate blood glucose in the setting of hypoglycemia is primarily CNS hypoglycemia. The body's measures which help to remedy hypoglycemia are primarily the release of epinephrine and glucagon with their effects being additive. The neonate requires a considerable amount of glucose, especially in the perioperative period. There is a significant decline in glycogen storage within the liver within the first 3 postnatal hours. If hypoglycemia is resistant to medical therapy, a laparotomy may be indicated to determine the presence of a tumor or subtotal pancreatectomy. Ketonic hypoglycemia is the most common form in children. 

Maximum effects of arginine vasopressin result in an osmolality of 1400 mOsmol/L with a urine output of 0.5 mL/kg/hour. It is important to initiate DDAVP treatment as soon as diabetes insipidus is made as the diagnosis, to prevent large surges in fluid loss. The goal is to double the urine osmolality in comparison to the plasma, and obtain a urine output of 2 CHAPTER 7: ENDOCRINE SYSTEM mL/kg/hour. Death can occur within 1-5 days after the presentation of diabetes insipidus with cerebral insult. Low urine osmolality (<300 mOsmol/L) and serum osmolality higher than 295 mOsmol/L is consistent with a diagnosis of diabetes insipidus without the presence of any osmotic diuretics. In the absence of ADH hormone, the urine flow will continue to increase in the range of 15-20 mL/kg/hour with a significant increase in serum osmolality. 15. C The daily requirement is approximately 0.3-0.4 mEq/kg/day intravenously. With a decrease in glomerular filtration rate, magnesium replacement may precipitate hypermagnesemia. Intravenous magnesium should not be given as a rapid bolus (as discussed previously). Magnesium chloride is preferable to magnesium sulphate because the sulphate can bind calcium. Rapid magnesium infusion leads to a poor clinical response because peak magnesium levels are associated with peak renal excretion. 20. D With long-term steroid use, morning administration will minimize hypothalamic-pituitary-adrenal axis suppression. Also, with prolonged use of the administration of steroids, it is best to administer the dose in the morning, because this will coincide with peak diurnal variation in the endogenous steroid levels. The 30-minute adrenocorticotropic hormone (ACTH) administration test is a reliable test for adrenal suppression. Prolonged use of 12 mg/m 2 /day of cortisol does not cause clinical significant hypothalamic-pituitaryadrenal axis suppression. Methylprednisolone does not interfere with the common radioimmune assay method of cortisol administration. Dexamethasone administration will not interfere with subsequent measurement of cortisol, and therefore, it is used in the so-called dexamethasone suppression test. 2. D The ebb phase and the flow phase are characteristic features of hypermetabolism and not features of a starvation syndrome. The ebb phase is similar to a shock stage during which the metabolic rate is slow. The flow phase is characterized by increased metabolism. Normally with aerobic glycolysis, the end product is pyruvate. Subsequently the end products enter the tricarboxylic acid cycle (kreb cycle) for production of the high-energy adenosine triphosphate. With substantial ketonemia, this process is inhibited, and therefore, utilization of glucose is impaired. 3. B During hypermetabolism, which is characterized by an initial ebb phase followed by a flow phase, there is usually an associated hyperglycemia owing to decreased sensitivity to the effect of insulin, although the level of insulin may actually be higher than usual. 6. E Preventive measures that are used for stress ulceration in the ICU include feeding, which by itself, acts as a protective barrier for the gastric mucosa, or the administration of H 2 blockers, which may be administered by continuous infusion. These would include ranitidine or famotidine. Administration of antacids has been shown to be as effective as H 2 blockers. Alternatives include administration of sucralfate, which has been shown to be comparable to H 2 blockers. Enteral feedings seem to stimulate release of the hormone gastrin. Administration of gastrin itself is not one of the measures that is clinically used in an ICU as a preventative measure against stress ulceration. (Rogers MC, et 10. D Vasopressin, an antidiuretic hormone, appears to be released during laparotomy and contributes to the decreased motility of the small bowel. Other contributing factors are hypokalemia, particularly with potassium levels of less than 2.5 mEq/L. The colon is the portion of the bowel most dependent on neural control to achieve motility. This is the portion of the bowel that is most sensitive to anesthesia-induced inhibition of motility, and the last to recover. The role that handling or direct manipulation of the gut plays in the development of ileus is not very clear. 12. D Postoperative intussusception that is usually ileoileal rather than ileocecal (which is seen in late infancy) is a problem that can be overlooked in the postoperative patient, particularly in patients who are receiving analgesia for postoperative care along with nasogastric suctioning to decompress the bowel. However, this is important to recognize to avoid morbidity and mortality. (Ein H, Ferguson J. J Pediatr Surg, 1971; 6:16.)

Please see the answer to Question 10.

14. D In the setting of postoperative ileus, if the cecum is very dilated, particularly if the diameter is greater than 12 cm, there is a very high risk of perforation even in the absence of mechanical obstruction. The only effective treatment for postoperative ileus is nasointestinal intubation to decompress the bowel and supportive measures. Neostigmine has not been shown to be a safe therapeutic intervention, and is associated with significant side effects. 16. C Clostridium difficile is an important infection to recognize in the ICU, particularly where broadspectrum antibiotics have been utilized. It presents with diarrhea, which can be bloody in nature and associated with significant volume loss. When this is diagnosed, usually by obtaining a toxin assay, oral vancomycin or intravenous metronidazole are usually effective. Stool culture for corona virus and rotavirus are important for epidemiological studies, but will not contribute to a patient's therapeutic intervention, nor do small bowel radiography or colonoscopy. (Viscidi RP. Pediatrics, 1981; 67:381.) 17. C Acute pancreatitis is a medical condition characterized by inflammation of the pancreas with subsequent release of the enzymes amylase and lipase. The degree of serum amylase does not seem to be proportional to the severity of acute pancreatitis. Serum lipase levels seem to be elevated for a longer period of time than serum amylase. Pancreatic trypsinogen serum levels seem to rise early in the course of pancreatitis and remain elevated for up to 5 days. In a clinical situation where amylase and lipase are normal and there is a high suspicion of pancreatitis, one could look at the level of trypsinogen. Some of the bad prognostic signs of acute pancreatitis include hyperglycemia, leukocytosis, hypocalcemia, and azotemia. 27. C Hepatorenal syndrome can develop in a setting of isovolemia. However, preventive measures that have been shown to be helpful for this clinical condition include avoiding large volume paracentesis in order to avoid intravascular volume depletion, as well as use of potent diuretics, which can also lead to intravascular volume depletion. Use of dopamine has not been shown to be effective for this clinical condition. In the early stages when this condition is suspected, expansion of intravascular volume with salt-poor albumin to raise the central venous pressure to the upper limits of normal is a helpful preventive measure. Other preventive measures include avoidance of prostaglandin antagonists, such as ibuprofen. 29. E Measures to decrease protein intake, as well as elimination of colonic bacteria by use of oral lactulose, oral antibiotics, such as neomycin, have been shown to be effective for HE. Use of hypertonic glucose to provide calories is also an important measure in the management of these patients. (Butterworth RF. Dig Dis Sci, 1992; 37: 321-327.) 30, 31. D, E In a patient with HE, there is inappropriate pathological cerebrovascular tone along with altered permeability of the blood-brain barrier that contributes to their symptomatology. In these patients, intracranial pressure monitoring along with hyperventilation to lower the PCO 2 will facilitate management. Steroids have not been shown to decrease mortality in these settings. These patients should be considered for hepatic transplantation and evaluated for this procedure in the initial stages of ICU admission because it has been shown that if the patient progresses to decorticate posturing and becomes ventilator dependent, it usually too late to initiate liver transplantation. 

A Liver disease is usually not homogenous, and therefore, drug metabolism is affected to a variable degree depending on the type of medication. It seems that the process of glucuronidation is more resistant to abnormalities in function than the process of oxidation, and therefore, in treating a patient with liver disease, preference should be given to drugs that are metabolized through this pathway. For drugs that undergo significant hepatic biotransformation clearance of these drugs tends to be proportional to the degree of liver blood flow. 38. C Medium-chain triglycerides (C 6 to C 12 ) inhibit gastric emptying less than long-chain fatty acids, and are absorbed from the GI tract faster than long-chain fatty acids. Consequently, they convert into energy more rapidly than the long-chain fatty acids, or long-chain triglycerides. Medium-chain triglycerides are absorbed directly into the systemic circulation through the portal venous system, instead of being absorbed through the lymphatic lacteals and subsequently into the thoracic duct. ( 1. E The developmental pattern of immunoglobulins (Igs) is as follows: IgG transfer across the placenta occurs as early as 8 weeks gestational age. Its level is directly proportional to gestational age, but is still less than 50% of term levels at 28 weeks gestation. The IgG levels fall during the first four months of extrauterine life reaching adult levels by 4-6 years of age. By the 10th week of gestation, the fetus is capable of producing IgM and may make large quantities in the presence of a congenital infection. IgA is not measurable until late in gestational life and is very limited in the infant, failing to reach adult values until puberty. 

C3a is an anaphylatoxin that induces smooth muscle contraction, histamine release from basophils and mast cells, and increased vascular permeability. The C5b-C9 components are referred to as 

can affect immune function. For example, N 2 O decreases both T-cell responses to mitogen, and B-cell proliferation and activity. Halothane decreases phagocytosis, bacterial killing, and chemotaxis and has a depressant effect on reticuloendothelial phagocytic activity. The administration of thiopental and other barbiturate agents at anesthetic levels for as little as 30 minutes can produce granulocytopenia. Longer exposures to pentobarbital have resulted in an 80% decrement in the circulating granulocyte count. The major adverse effect on immunity produced by narcotics, such as morphine sulfate, is depression of leukocyte chemotaxis. A surgical wound dramatically increases the circulating neutrophil count. This is related to certain humoral effects of trauma, most notably, a strong, acute catecholamine release that is one component of the body's nonspecific response to stress. Blood levels of B-lymphocytes and T-lymphocytes decrease in response to surgical stress. ( 

B Secretory IgA appears later than serum IgA (already limited in the infant; see Question 1). Diseases whose defense depends primarily upon secretory IgA, such as some of the viral respiratory agents (e.g., respiratory syncytial virus) and infectious diarrheas, remain prevalent throughout infancy. The infant is at risk for encapsulated organisms and cannot localize infections well. IgM production by the non-infected newborn does not reach adult levels until 1-2 years of life. 9. B, C, A As mentioned earlier, in the early postburn period, Gram-positive organism infections predominate. The most likely organism is Staphylococcus aureus, which has an insidious course, and is associated with a low mortality. Of the Gram-negative organisms that later colonize the wound, Pseudomonas aeruginosa and E. coli are the most prevalent. Pseudomonas infection can be particularly dangerous because it has a propensity to further devitalize intact tissue, and may convert a partial thickness burn to a full thickness one. Candida albicans and other Candida species can cause some of the most severe infections, and are associated with the highest mortality. 

Marasmus (protein and calorie deficiency) have more significant effects on cell-mediated immunity. Children with kwashiorkor have very small thymus glands, with relative atrophy of lymph nodes and spleen. Qualitatively, this is expressed as an increased incidence of infections with viral (especially measles and disseminated herpes), fungal (Candida), and opportunistic organisms (Pneumocystis carinii). In kwashiorkor, the thymus is typically small. The B-cell system is relatively spared in children with protein calorie malnutrition. Seroconversion in response to immunization with diphtheria and tetanus toxoids, pneumococcal polysaccharide, and polio vaccines is normal even in malnour- 14. D Asplenia in children can result from a variety of conditions ranging from trauma to sickle cell disease. This makes the ability to perform randomized clinical studies of asplenia difficult. Congenital asple-nia is most often associated with cardiac abnormalities (heterotaxy). Absence of the spleen, whether anatomic or functional, predisposes the young child to potentially fatal sepsis from encapsulated bacterial species. The most prevalent offender is the pneumococcus in 50% of cases. Haemophilus influenzae type B, meningococcus, and group A streptococci account for 25%. There is general agreement that immunization of asplenic patients with pneumococcal vaccine should be performed. Children who are less than 2 years of age have a poor response to pure polysaccharide vaccines, so immunization at a young age is not feasible. Although penicillin prophylaxis has become routine, others have suggested that prompt administration of antibiotics with any febrile illness will more reliably reduce the percentage of fatal episodes. 

Syndrome is an X-linked recessive disorder manifested by eczema, thrombocytopenia, and recurrent infections with encapsulated bacteria. The disorder is related to an inability to produce antibody to polysaccharide capsule. Serum immunoglobulins show a decrease in IgM, with an increase in IgA and IgE. Ataxia-Telangiectasia is an autosomal recessive disorder involving 11q22-23. The disorder results from a defect in DNA recombination. Breakpoints involve genes that encode for T-cell receptors. Associated conditions include IgA deficiency and lymphosarcoma. Chronic granulomatous disease involves a defect in any one of the four components of the enzyme NADPH oxidase, essential for bacterial killing in the neutrophil. 65% are X-linked, and the remainder are autosomal recessive. Organisms that are catalase-positive (S. aureus) can produce chronic infection by preventing phagocytes from using microbial generated hydrogen peroxide. Chediak-Higashi Syn-drome involves defective chemotaxis, phagocytosis, and natural-killer (NK) activity because of elevated levels of cyclic adenosine monophosphate. Abnormal giant granules formed by the fusion of lysosomes are seen in cells that contain lysosomes. The clinical characteristics include recurrent pyogenic infections, albinism, photophobia, and nystagmus. Schwachman-Diamond Syndrome is a disorder that involves deficiency of the exocrine function of the pancreas and neutropenia secondary to bone marrow failure. 18. C Childhood sexual abuse and undetermined risk factors account for less than 1% of pediatric AIDS cases. Perinatal transmission from infected mother to infant is the most common means by which children acquire HIV infection. HIV antibody screening of all donated blood products, as well as donor self-exclusion programs, were initiated in the early 1980s has lead to a finite risk of transmission from infected blood products. Enzyme-linked immunosorbent assay (ELISA) is the primary screening test for HIV infection because of its very high degree of sensitivity, reproducibility, and low cost. 

Among perinatally infected children, the earliest clinical manifestations includelymphadenopathy, hepatosplenomegaly, hypergammaglobulinemia, and skin disease including candidal dermatitis or seborrhea. ELISA is the primary screening test for HIV infection because of its very high degree of sensitivity, reproducibility, and low cost. The ELISA detects antibodies to HIV usually within 6-12 weeks of the primary infection. Western blot is the most widely used confirmatory test for HIV. The Western blot detects viral protein antigens. In infants younger than 18 months of age, serum tests for IgG antibody to HIV do not differentiate between infant and passively acquired maternal antibody. Polymerase chain reaction permits amplification of HIV viral DNA. This process is as sensitive and specific as viral culture. Hypergammaglobulinemia, not hypogammaglobulinemia is an early clinical manifestation of HIV infection. 

In series that include asymptomatic, mildly symptomatic, and children with advanced neurological disease, a 19.6% prevalence rate of HIV encephalopathy is reported. Although rare, primary CNS lymphomas are the most common intracranial mass lesions that develop in HIV-infected children. In a multicenter study sponsored by the National Institute of Child Health and Human Development, intravenous Ig-treated children with CD4 counts higher than 200/mm 3 3. C In a newborn who develops significant seizures within the first 24 hours after birth, prior to having consumed a significant amount of protein in the diet, and who does not have significant metabolic acidosis or elevation of ammonia levels, one has to think about nonketotic hyperglycinemia. Ornithine transcarbamylase deficiency is an X-linked disorder of ureacyte and is usually associated with significant elevation of blood ammonia levels. Methylmalmic acidemia, propionic acidemia, and isovolemic acidemia are organic acid disorders and are usually characterized by HAGMA. Maple syrup urine disease is discussed in Question 1, and is a disorder of branched chain amino acids caused by defective branched chain ketoacid dehydrogenase. Management of glucose and pH is most important in these patients. 

A Hypoglycemia produces selective necrosis of the superficial cortical layers sparing the non-neuronal elements (unless hypoglycemia is profound and prolonged). Infarction is usually absent even after severe hypoglycemia. In Reye's syndrome, nonspecific cytotoxic cerebral edema is seen with swelling of astrocyte foot processes. The hallmark of HE is proliferation and enlargement of the so-called Alzheimer -type astrocyte, which is basically a protoplasmic astrocyte. Longstanding heparin encephalopathy has been shown to be associated with degenervation changes in layers 5 and 6t of the cerebral cortex. 9. B, A, D, C Diabetic ketoacidosis or any acute metabolic acidosis state will decrease PCO 2 by 1-1.5 mmHg for each millimole change in bicarbonate concentration. In severe scoliosis, there is retraction of the chest wall causing chronic alveolar hypoventilation, with the development of chronic respiratory acidosis. A bicarbonate rise of 4 mmol will occur with a rise in 10 mmHg of PCO 2 . Here both pH and bicarbonate concentrations are higher than expected for the level of PCO 2 elevation suggesting a mixed acid base disorder-metabolic acidosis superimposed or chronic respiratory acidosis. Botulism will cause rapid onset of respiratory failure causing pure respiratory acidosis. In acute respiratory acidosis, the pH will fall by approximately 0.08 U for each 10 mmHg of PCO 2 . Plasma bicarbonate will increase 1 mmol/L for each increase of 10 mmHg in PCO 2 . Salicylate intoxication causes acute metabolic acidosis. It also stimulates the respiratory center causing coincident respiratory alkalosis. A decrease in PCO 2 is out of proportion to the fall in plasma bicarbonate, which is suggestive of mixed acid-base disorder-metabolic acidosis and respiratory alkalosis. 11. C Nearly all critically-ill patients have decreased serum levels of T3 and 50% have a decrease in the level of T4 concentration with normal or low thyroid-stimulating hormone (TSH). The reduction in T3 levels results from a decrease in deiodinase activity that occurs in critical illness. This is reflected in the increase in serum level of T3 that occurs during critical illness. This enzyme is responsible for the degradation reverse of T3, explaining the increase in serum levels of reverse T3 that occurs in critical illness. 2. D The μ receptor agonists are the most commonly used opioids for analgesia. The μ 1 receptor is the subtype that provides supraspinal analgesia. The μ 2 receptor produces respiratory depression, inhibition of GI motility, and spinal analgesia. Furthermore, the μ 2 receptors cause bradycardia and sedation. Newborns may be sensitive to an age-related receptor phenomenon that leads to opiate-induced respiratory depression. 

The μ 2 receptor inhibits GI motility. Methadone, morphine, fentanyl, and meperidine are agonists for the μ receptor. The κ receptor inhibits antidiuretic hormone release. The δ receptor produces analgesia, respiratory depression, euphoria, and physical dependence. The psychotomimetic effects that are observed with some opiates including dysphoria and hallucinations are associated with the σ receptor. Phencyclidine is an agonist for the σ receptor. Meperidine is also associated with seizure activity. This, however, can occur in any age group and is related to the buildup of the toxic metabolite normeperidine. The serotonin syndrome occurs following the use of serotomimetic agents of which meperidine is included. When used alone or in combination with monoamine oxidase inhibitors a symptom complex characterized by myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing, and rarely, rhabdomyolysis and death can occur. The development of chest wall rigidity is a side effect associated with the rapid administration of fentanyl. This effect can be treated with the administration of either a neuromuscular blocker or naloxone. 6. B Fentanyl is approximately 100 times more potent than morphine and is largely devoid of hypnotic or sedative activity. Sufentanil is approximately 10 times more potent than fentanyl. Alfentanil is approximately 10 times less potent than fentanyl. The α-1 acid glycoprotein is an acute phase protein that inhibits platelet aggregation and phagocytosis, and may help to regulate collagen fiber formation in healing. 11. D Naloxone is a nonselective, opioid antagonist that works in small doses to alleviate the respiratory depression associated with opioids without affecting the analgesic properties. It is rapidly metabolized in the liver. Naloxone has no effect on the mental status of patients who have not received opioids. 

Ketamine is a ventilatory depressant that reduces the ventilatory response to carbon dioxide. Laryngeal reflexes remain intact but this does not preclude the potential for aspiration. Ketamine increases pulmonary compliance by direct action on bronchial smooth muscle and indirectly by increasing plasma catecholamine levels. The drug is highly lipid soluble. Its redistribution rather than biotransformation or elimination is responsible for its short half-life. 14. E The local anesthetics are of two types, amides and esters, which are both weak bases that block nerve conduction at the sodium channel when they are in their ionized form. In order to gain access to the channel, the drug must cross the membrane. It does this in its ionized form. The minimum concentration of a local anesthetic is the concentration necessary to block nerve impulse conduction. Unmyelinated nerve fibers carry nociceptive information and have a lower minimum concentration than heavily myelinated fibers. Less local anesthetic is necessary to block the transmission of pain than is necessary to produce muscle paralysis. ( 16. E GABA is the major inhibitory neurotransmitter in the brain. Glycine is an inhibitory neurotransmitter in the spinal cord and brainstem. The GABA receptor has two α and two β subunits. Binding of benzodiazepines to the α subunits of the GABA receptor facilitates binding to the β-receptors and promotes membrane hyperpolarization and resistance to neuronal excitation. The benzodiazepines can blunt or abolish the respiratory responses to hypercarbia and hypoxia. They produce hypoventilation by reducing tidal volume. The benzodiazepines produce minimal cardiac affects. However, they do reduce preload and afterload. They increase, rather than decrease coronary sinus blood flow and myocardial oxygen consumption. 3. C First one has to calculate the creatinine clearance, which is = L × K / serum creatinine, where L is length of the child, K is a constant and it equals .45 for this age. Therefore, the creatinine clearance for this patient = 75 × 0.45 / 1.2. Assuming that the normal creatinine clearance is 100 mL/minute/1.73 M 2 , the renal index would = 28.1 mL/minute, which is equal to 0. 4. E Patients at risk of adrenal hypofunction who are admitted to the PICU (for nontrivial illness) require additional doses of corticosteroid coverage. The physiological dose is 12.5 mg/M 2 body surface area (BSA)/day of hydrocortisone. Patients with a febrile illness presumed to be secondary to a nontrivial infection, deserve doubling of the maintenance dose. Patients with a major trauma, major surgery, or generalized sepsis deserve 3-4 times the maintenance dose. When time allows, high-dose corticosteroids must be initiated 1-2 days prior to surgery, and weaned over a period of 5-7 days. Because the risk of undertreatment is higher than overtreatment in patients with a serious illness or trauma, it is reasonable for a clinician to administer 100-200 mg/M 2 BSA/day of hydrocortisone to these patients. Gastric acidity partially inactivates oral steroids and, therefore, higher doses are often necessary. ( 

Adrenergic receptors comprise four subtypes: α 1 , α 2 , β 1 , and β 2 . Each of these subtypes and the family keeps growing. α 1 Receptors are typical postsynaptic receptors, mediating smooth muscle contraction in both the vascular tree (causing intense vasoconstriction) and the genitourinary system. α 2 Receptors include presynaptic and nonsynaptic sites (such as on platelets). α 2 Receptors tend to inhibit release of norepinephrine from sympathetic nerve terminals resulting in relaxation of vascular and GI tract (GIT) smooth muscles. Phenoxybenzamine, or α 1 blocking agent, is the most selective α 1 blocking agent, and is used for preoperative management of patients with pheochromocytoma. Prazosin is a potent but less selective α blocker, and its blockade of α 2 receptors (presynaptic receptors) cause uninhibited release of norepinephrine, thus counterbalancing the α 1 receptor blockade. Phentolamine is likewise not a selective α 1 blocker. Atenolol is a selective 6. E Cocaine is absorbed from respiratory, GIT, and genitourinary mucosa. It is metabolized in the liver by esterases. It is metabolized by plasma pseudocholinesterase and nonenzymatic hydrolysis. The two major cocaine metabolites in urine are benzoylecgonine and ecgonine methyl ester. Most urine drug screening tests detect benzoylecgonine. There is a greater potential for toxicity in patients with pseudocholinesterase deficiency because cocaine will be less metabolized. Drug abusers ingest an organophosphate in an attempt to prolong the effects of cocaine, which also increases the risk of cocaine toxicity. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 855-856.) 7. D Deferoxamine does interfere with subsequent laboratory determination of iron level, and under these circumstances, the most accurate method of measuring serum iron is using the atomic absorption spectrophotometric method. Interestingly, deferoxamine actually potentiates the activity of Yersinia enterocolitis. Children usually require 24 hours or less of deferoxamine therapy. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 532-534.) 8-9. E, E Numerous substitutions of the phenylethylamine structure are possible resulting in different amphetamine-like compounds. These are referred to as amphetamines, although a more precise name, phenylethylamines, exists. The diagnosis of amphetamine overdose depends on a high degree of suspicion along with clinical judgment. Diagnosis by history alone is rarely helpful. There is no reliable blood analysis test and the quantitative urine test is not particularly useful for acute settings. One of the major differentiating features between cocaine and amphetamines is the duration of action, which lasts for about 2 hours in the case of cocaine. The half-life of amphetamines on the other hand ranges from 8 to 30 hours. Amphetamines enhance the release of, and block the reuptake of, catecholamines, resulting in excess stimulation of both α and β receptors. At higher doses, they can cause release of serotonin. The clinical manifestations are that of cardiovascular and CNS excitation. Do not neglect to obtain a rectal temperature in these patients. Hyperthermia, if not recognized and treated aggressively, may be rapidly fatal in association with delirium. These patients are often very agitated and require sedation because agitation against restraints may exacerbate the associated rhabdomyolysis. Benzodiazepines are the drug of choice because neuroleptic agents lower seizure threshold, alter temperature regulation, and may induce dystonia. Death is often from hyperthermia, dysrhythmias, or intracerebral hemorrhage. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 863-869.) 10-16. B, A, C, C, D, D, E Any child who has ingested more than 20 mg/kg body weight of elemental iron and who has not vomited spontaneously (and is awake) may be given syrup of ipecac and brought to the emergency department. If GI symptoms develop within 6 hours in these children or children who have ingested less than 20 mg/kg body weight of elemental iron and have a level of less than 500 mg/dL of serum iron, they may be discharged home because it is unlikely that children who present within 1 hour of ingestion, and who have not vomited, may benefit from ipecac (if not already given at home), as adult-strength pills are too large to be removed by lavage. Lavage may be performed if chewable forms are ingested or if pill fragments are seen in the vomitus or on the abdominal radiograph.

The properties of iron that promote its toxicity include: (1) first order or concentration dependent absorption that is seen even in the overdose setting, (2) absorbed iron cannot be rapidly excreted. Patients with massive overdose by history or clinical manifestations should be presumed to have taken a significant ingestion prior to determination of serum iron levels. The most valuable time to assess serum iron is 4-6 hours after ingestion. At this time, tablet breakdown is almost complete, but iron has not been completely distributed to tissues.

Because administration of deferoxamine (DFO) interferes with the standard calorimetric method of iron measurement, the laboratory must be informed of this fact. In this case, atomic absorption method is an accurate method and overcomes the false-negative results associated with the former test. DFO is a specific ironbinding agent that binds free inorganic iron to form ferrioxamine (which is reddish in color) that is excreted in urine. It is given intravenously because GIT absorption is poor. The efficacy of DFO is not explainable entirely on the basis of the amount of iron excreted. Therefore, it is possible that toxicity is prevented by making iron less available for cellular binding where toxicity occurs. Hb, cytochrome, and other protein-bound iron are not chelated. Activated charcoal is ineffective in the setting of iron poisoning, as are any of the lavage solutions that could theoretically bind the iron in the stomach.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 523-530.)

The major metabolic pathway for elimination of salicylates when therapeutic doses are used is conversion to salicyluric acid and salicylphenolic glucuronide. However, this metabolic pathway follows the Michaelis-Menten kinetics, which is a saturable form of kinetics. Therefore, in the setting of overdose, this metabolic pathway becomes completely saturated and an alternative pathway has to be available for metabolism of salicylate. This alternative pathway is option E (salicylate excretion unchanged in urine), and therefore, this route of elimination becomes of paramount importance during salicylate intoxication. Because two of the major pathways become saturated, the half-life increases from 2 to 4 hours at therapeutic doses to as long as 20 hours. Also, protein binding decreases from 90% at therapeutic levels to less than 75% at toxic levels, and Vd increases from 0.2 to 0.3 L/kg. A nomogram is of limited value and was developed to be used only 6 hours or more after a single ingestion of nonenteric coated aspirin when blood pH is known to be 7.4. Repeat testing of serum salicylate levels is mandatory every 2-4 hours after ingestion. In children, the respiratory alkalosis is transient and usually occurs with metabolic acidosis.

Respiratory acidosis with salicylate toxicity warrants an evaluation for another toxin or for pulmonary dysfunction, such as pulmonary edema, which is a rare complication of salicylate overdose. Alteration in mental status in the presence of metabolic derangements make pure acetaminophen overdose suspect, and elevation of temperature directly resulting from salicylate toxicity is an indication of severe toxicity, and often is a preterminal condition in the adult population.

Aspirin was the leading cause of child poisoning in the past; however, the incidence of poisoning resulting from aspirin has been declining over the last several years. Because acidemia tends to affect the protein binding of salicylate, hyperventilation to maintain some degree of alkalemia is clinically important in salicylate poisoning. Because salicylates are a weak acid, salicylates are ionized and less mobile in an alkaline environment, whereas with acidemia, more salicylate leaves the blood and enters the cerebral spinal fluid.

In the setting of hypokalemia, it is often difficult to achieve alkalinization because under these circumstances, there is a limitation on excretion of hydrogen ion into the tubular lumen, and one has to correct the hypokalemia in order to be able to achieve alkalinization of the urine.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 501-510.) 24-32. D, A, D, C, E,E, C, D, E Acetaminophen (N-acetyl-P-aminophenol [APAP]) is rapidly absorbed from GIT and peak plasma levels almost always occur within 4 hours of ingestion. The drug is metabolized in the liver by: (1) sulfation; (2) glucuronidation, (3) p-450 oxidase system, producing the intermediate metabolite (NAPQI) thought to be responsible for the toxicity; NAPQI is normally detoxified by conjugation with reduced glutathione and excreted in urine as mercapturic acid or cysteine conjugates.

A small fraction of acetaminophen is excreted in urine unchanged. This and the product of sulfation and glucuronidation are nontoxic. In the setting of overdose, when more than 70% of glutathione is depleted, NAPQI binds covalently to hepatocytes, inducing hepatic necrosis, which is usually centrilobular with periportal sparing. Children seem to be more resistant to the toxicity of acetaminophen, presumably because of the higher activity of the sulfation pathway. One exceptional group is children on anti-convulsants, such as phenobarbital, which accelerates the p-450 mixedfunction oxidase system with production of higher lev-els of NAPQI, which is the main metabolite responsible for toxicity. These children are a higher risk and must be treated at a lower level of serum acetaminophen.

Because APAP is so rapidly absorbed through the GIT, gastric emptying is of benefit only in the first 2 hours after ingestion. Because APAP is effectively absorbed to activated charcoal and also because binding of N-acetylcysteine (NAC) to charcoal is probably clinically insignificant, most physicians would use activated charcoal with NAC, with possible repeating of the loading dose of NAC. NAC is taken up by the hepatocytes and acts as a precursor for glutathione and sulfate, replenishing reduced glutathione. When given more than 24 hours after ingestion of APAP, NAC acts as an antioxidant. NAC is administered when APAP is in the toxic range based on the Rumack and Mathew nomogram. NAC is also indicated when (1) initial AST and prothrombin time are elevated, suggesting significant ingestion, (2) when there is a history of prior or present vomiting with ingestion of more than 140 mg/kg body weight, or (3) when there is a history of a large APAP ingestion at an unknown time.

The clinical manifestations of APAP toxicity is divided into four phases: Phase I is characterized by nausea, vomiting, and malaise; phase II is characterized by hepatic dysfunction; phase III is characterized by sequelae of significant hepatic dysfunction with jaundice and coagulopathy; and phase IV occurs if phase III is not reversible.

In younger children with significant toxicity, hypotension, hypothermia, and apnea may be noted. Liver enzymes (alanine aminotranferease and aspartate aminotransferase), bilirubin and prothrombin time and partial thromboplastin time should be measured every 24 hours for 4 days while therapy proceeds. It is important to recognize that APAP measured by the calorimetric method is unreliable in the presence of high salicylates, bilirubin levels, or renal failure. In these circumstances, high-pressure liquid chromatography and enzyme immunoassay may be employed.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 487-495.) 33, 34. E, C An acutely poisoned patient with a very high level of theophylline may be awake, alert, and merely tachycardic. If this patient does not exhibit tachycardia, the diagnosis of theophylline overdose is suspect or concurrent ingestion should be excluded.

The cardiac toxicity is owing to massive catecholamine (release of epinephrine and norepinephrine) stimulation of the myocardium and is aggravated by hypokalemia, hypercalcemia, and hypophosphatemia. β-Adrenergic stimulation is responsible for the electrolyte abnormalities, acid-base disturbances, and vasodilation. Metabolic acidosis, hypokalemia, and hyperglycemia are recognized features. The hypokalemia is from a transcellular shift (into the skeletal muscles).

The cardiovascular toxicity (dysrhythmias and hypotension) is worsened by hypoxia and co-administration of medications with b-adrenergic or anticholinergic activity. Anti-emetics with anticholinergic activity may worsen dysrhythmias, and if a pressor is used to elevate blood pressure, a pure a-adrenergic agent is preferred.

Massive theophylline toxicity can be effectively treated by hemoperfusion, and therefore, strong consideration should be given to initiating transfer of this patient to a facility with these capabilities, while the patient is still stable. At this same time, multiple doseactivated charcoal, intravenous β-blockers, and other supportive measures should be continued. The indications for initiation of hemoperfusion include a theophylline level greater than 90 mg/mL at any time; a theophylline level of more than 70 mg/mL 4 hours after ingestion of a sustained release tablet; and a theophylline level of more than 40 mg/mL with seizures, hypotension, or dysrhythmias. The author has treated a 2-year-old child with a theophylline level of 120 mg/mL without hemoperfusion.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 567-574.) 

With methanol intoxication, the onset of toxic symptoms or the development of metabolic acidosis is often delayed for 24 hours, with a range of 1-72 hours from the time of ingestion. Methanol is converted to formaldehyde and then formic acid (FA). The latter is responsible for the toxicity of methanol particularly with late recognition, with subsequent build-up of FA. Two factors that correlate best with poor outcome are: (1) delay of appearance of toxic symptoms for longer than 10 hours, and (2) elevated levels of FA. Clinically, the most characteristic clinical findings are symptoms of blurred vision (the sign of dilated pupils with sluggish response to light) and hyperemia of the optic disc. These features correlate best with metabolic acidosis.

Oxalaturia and elevated levels of glycolic acid are features of ethylene glycol (EG) poisoning. HAGMA and hyperventilation are features of both. The degree of AG or EG poisoning is the largest seen in any metabolic acidosis. However, the onset of high AG metabolic acidosis may be delayed, and therefore, if the clinical suspicion is high, ethanol therapy should be initiated promptly. Because ethanol has a greater affinity for alcohol dehydrogenase than either methanol or EG, when ethanol is administered in sufficient concentration (100-150 mg/dL), it competitively inhibits formation of toxic metabolites, allowing the primary alcohol to be eliminated in urine unchanged. An optimal blood ethanol level, 100-150 mg/dL, should be attained, either orally (using a 15-20% concentration) or intravenously using a 10% concentration. Ethanol should be continued during hemodialysis at a higher dose because ethanol itself is dialyzable.

Alkalinization with NaHCO 3 is also helpful because renal clearance of glycolic acid is enhanced and the amount of undissociated FA is decreased at a higher pH, thereby limiting access to the CNS.

Additional therapeutic measures EG ingestion may include 100 mg of thiamine intravenously or 50 mg of pyridoxine intravenously every 6 hours until acidosis is resolved and EG level is zero. Pyridoxine in the presence of magnesium may shunt the metabolism of EG metabolites from glycolic acid to the harmless glycine, and thiamine may reduce production of oxalic acid.

For methanol intoxication, 50-75 mg of folic acid every 4 hours for 24 hours has been suggested. Folic acid may enhance the elimination of FA.

(Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 827-836.) 53, 54. C, C The typical initial dose of naloxone in an adolescent is approximately 2 mg intravenously. If the first dose of naloxone fails to reverse symptoms, then 2-4 mg intravenously should be given up to a total dose of 10-20 mg. In a setting where there is no ventilatory insufficiency, it is not essential to initiate high-dose naloxone. Once the patient responds, two-thirds of the dose that reversed the respiratory depression needs to be used on an hourly basis until the patient recovers. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 26,27, 100, 422,  770- Many of the signs noted during toxicity are caused by central and peripheral anticholinergic effects, which include agitation, confusion, hallucinations, coma, seizures (central), tachycardia, hypertension, hyperthermia, dry skin, and urinary retention (peripheral).

Cyclic antidepressants are divided into first-generation (or tricyclic) antidepressants and second-generation (or cyclic) antidepressants. These drugs have a more specific mechanism of action but their toxicity profile remains the same. Patients with antidepressant overdose often develop wide, complex dysrhythmias, hypotension, and seizures within minutes of ingestion. If a life-threatening event is going to occur, it will occur within the first 6 hours of hospitalization (most often within 2 hours of admission to the emergency department). After initial stabilization, a 12-lead EKG should be obtained and the patient placed on cardiac monitor. The finding of a small S-wave in leads I and AVL and a small R-wave in AVR along with a prolonged QT and sinus tachycardia are highly specific and sensitive for cyclic antidepressants (CAs). However, absence of these EKG changes does not exclude a cyclic antidepressant overdose (CAO). The duration of QRS has been shown to be prognostic of seizures and dysrhythmias: QRS greater than 100 msec, 30% risk of seizures; QRS more than 160 ms, 50% risk of dysrhythmias. Blood should be sent for electrolytes, glucose, and if ingestion was intentional, an acetaminophen level. It is not clinically useful or cost-effective to obtain a plasma cyclic antidepressant level because there is no good correlation between levels and symptomatology. However, with levels exceeding 1000 mg/mL, dysrhythmias and seizures are usually seen.

CAs have a membrane depressant effect on the myocardium by slowing sodium influx into the myocardium during phase 0 of depolarization. This leads to intraventricular conduction defects, dysrhythmias, decreased cardiac output, hypotension, and decreased coronary perfusion. The effects of CAs on sodium channels can be attenuated by increasing the blood pH to 7.50-7.55, either by hyperventilation or Na + HCO 3 . At this pH, it appears that CA uncoupled from sodium channels, whereas hypotension and acidosis enhance their binding. (Lidocaine may also be effective in treating ventricular dysrhythmias.) Therefore, aggressive treatment of hypotension and metabolic acidosis is essential. If hypotension does not respond to fluid resuscitation, then depending on the underlying etiology, inotropic support or vasopressors may be used. Norepinephrine will increase the vascular tone, whereas dobutamine will increase the contractility without increasing the vascular resistance dramatically. Dopamine should be in this setting because of its arrhythmogenic potential.

Seizures that develop in the setting of CAO are usually brief and respond to lorazepam. For persistent seizures, phenobarbital is recommended. Phenytoin is not recommended because of the potential for dysrhythmias. Other drugs that must be avoided include: class IA and IC antiarrhythmias (membrane stabilizers); propanolol and verapamil (myocardial depressants); flumazenil (inhibits the chloride channel of α-adrenergic and β-adrenergic receptors similar to CA). Because of the rapid deterioration of mental status in patients with CAO, ipecac should not be used. Multiple dose charcoal does enhance elimination of CA and physostigmine has not been shown to be safe and/or effective in this setting.

(Goldfrank, LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 726-731.) 60. A, B, C, D These are the drugs/toxins that should be in the differential diagnosis of HAGMA: a. Paraldehyde ingestion can be diagnosed by its distinctive pungent odor. Other findings include: gastritis, mental status changes with possible coma, tubular acidosis, azotemia, oliguria, and proteinuria. b. Toluene abuse by inhalation takes two forms:

i. Huffers inhale from a toluene-soaked cloth. ii. Baggers inhale from a plastic bag containing toluene placed over the head. 

During hemoperfusion, compounds are cleared from blood as they come in contact with an adsorbent (surface) material contained in a cartridge, within an extracorporeal circuit. The adsorbent material could be: (1) Charcoal-best for polar compounds, such as salicylates, or (2) Amberlite XAD-4-best for lipid soluble compounds, such as theophylline, phenobarbital, CAs, meprobamate, and digoxin.

Extraction of many of these compounds is almost complete and the clearance often equals the blood flow through the circuit. Many of the pharmacokinetic factors that limit the applicability of diagnosis are not significant during hemoperfusion. Thus, molecular weight, degree of protein, binding in the plasma, and water solubility are not limiting factors during hemoperfusion because of the high adsorbent area that comes in contact with the blood. The Vd remains important however. Drugs with a large Vd may be completely extracted from the blood as they pass through the adsorbent, but if only a small amount is present in the plasma compartment, only a small total amount may be removed from the body. 68. D P Ka is an important concept in pharmacology particularly in the setting of overdose. For example, with salicylates, which have a P Ka of 3.1 at a pH of 3.0, the ratio of ionized to non-ionized is 1:1. However, if the pH is increased to 7.4, the ratio of ionized to nonionized increases to 2500:1, and this will dramatically help with elimination of the drug through the kidneys. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 503-505.) 69. D Because K + is exchanged with H + in the renal tubules, hypokalemia with total body K + deficit will hinder urinary alkalinization. (Goldfrank LR. Goldfrank's Toxicologic Emergencies, 6th Edition; pp. 503-510.)

70. E For a compound to be dialyzed efficiently, it must be poorly protein bound (<90%) and highly water soluble, have a small Vd so that the majority of the drug is in the plasma, and have a small molecular-weight; compounds with a molecular-weight higher than 500 are progressively less dialyzable. ( 75. E Activated charcoal should be administered in almost all cases of poisoning after emesis and lavage are accomplished. Exceptions are in cases of ingestion of (1) Corrosives-whether alkaline or acids, as charcoal does not absorb either one effectively and the dark charcoal may interfere with endoscopic examination; (2) Anticholinergics-overdose with ileus is an obvious situation when repeated dose-activated charcoal should not be used; 2. C Catecholamines produce hyperglycemia, hyperlipidemia, increased oxygen consumption, and hyperkalemia, and α-stimulation reduces insulin and glucagon secretion. The overall effect of catecholamines on the islet cells it to not only increase glucagon, but also decrease insulin secretion. Cortisol decreases the peripheral utilization of glucose but the increase in plasma cortisol is designed to produce an increase in osmolality in response to hemorrhage. 7. C In Weil's 5-2 or 7-3 rule, the 5-2 applies to the central venous pressure (CVP), and the 7-3 rule applies to the pulmonary capillary wedge pressure (PCWP). Volume boluses are administered and the pressure response is measured. When the CVP is less than 8 or the PCWP is less than 12, 10-20 mL/kg of isotonic solution is infused over 10-15 minutes. If the CVP increases by more than 5 or the PCWP increases by more than 7, the infusion is stopped. Immediate fasciotomy is indicated when a pressure greater than 60 cm H 2 O is present. 14. E Pulmonary dysfunction after thermal injury may be secondary to inhalational injury, aspiration, shock, sepsis, congestive heart failure, or trauma. The presence of inhalational injury increases mortality by 20%, whereas pneumonia increases the risk of mortality by 40% in burn patients. In the resuscitation phase of burn injury, lung injury results from hypoxia and subsequent reoxygenation, CO and cyanide toxicity, airway edema, chest wall, and pulmonary compliance problems. Hypoproteinemia may contribute to edema formation in the postresuscitative phase. Hepatic dysfunction is commonly encountered in thermal injury, and can generally be found in more than 50% of patients. Thrombocytopenia appears first, then is followed by thrombocytosis several days later. Significant increases in fibrinogen, Factors V and VIII occur. RBC mass decreases. Hypoxia occurring in the first 48 hours was the most common cause of encephalopathy and was related to smoke and CO inhalation sustained in enclosed fires. Acalculous cholecystitis is of two types in the burn patient. The first involves bacterial seeding in septic patients and the second arises in patients with dehydration, ileus, or pancreatitis in whom the gallbladder is distended with sterile fluid. Burn-injured patients are immunocompro- First-degree burns are superficial burns isolated to the epithelial cells and characterized by erythema and mild blistering. Second-degree burns involve a tissue depth into the dermis. A superficial partial-thickness burn is moist, red, and tender. It becomes pale, but dermal papillae can be visualized through the eschar within a few days. Third-degree burns extend through all layers of the skin and invade the hypodermic fat. 17. B With the Rule of 9's, the front and back are each assigned 18% of BSA; each arm is assigned 9%; each leg is assigned 18%. Therefore, a burn that involves 9% (arm), plus 18% (leg), plus 18% (back), equals 45% total BSA burn. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; p. 1526.)

A minor burn involves less than 5% of the BSA and no significant involvement of the hands, feet, face, or perineum. A moderate sized burn involves between 5 and 15% of the body surface area. Alternatively, any full-thickness component also qualifies. Involvement of the hands, face, feet, perineum, or the presence of a complicating factor, such as chemical or electrical injury, also constitutes a moderate burn. A severe burn is characterized by more than 15% total BSA burn or the presence of smoke inhalation or CO poisoning. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; p. 1526, figure 45.2.) 19. B House fires account for 84% of burn associated fatalities, the cause of which is most frequently smoke inhalation rather than tissue damage from flames. Chemical burns should be flushed with water for 20-30 minutes, not alcohol. Tetanus prophylaxis must be addressed in all burn patients. Scald burns are the most common type of pediatric burn and the home is the most common location. ( 20. E The criteria for transfer to a burn center include significant underlying disease, associated inhalation injury, 10% BSA or more of partial or thirddegree burns in children younger than 10 years of age or more than 20% BSA in children older than 10 years of age, third-degree burns more than 5% in any age group, electrical and chemical burns, and burns associated with major trauma. 

Systemic blood pressure is usually maintained after thermal injury despite hypovolemia, thereby making blood pressure an insensitive measure of volume status. Generally, children with less than 5% of their BSA burned do not require intravenous fluid therapy. Children with a burn exceeding 15% BSA will require intravenous resuscitation. If the burn size exceeds 30% BSA, placement of a central venous catheter is recommended. Muscle relaxants and sedation are contraindicated in the child who has signs of upper airway obstruction up until the airway is secured. 

Mafenide is an excellent antibacterial. It inhibits carbonic anhydrase and may lead to acidosis. It can be painful, but penetrates the eschar rapidly. It is applied twice daily. Silver sulfadiazine is a broad antibacterial agent that is painless. It penetrates fairly well through the eschar. It is contraindicated in pregnancy and has unknown absorptive properties in the fetus. Bacitracin is limited in its antibacterial action, has poor eschar penetration, but is easy to apply and cosmetically acceptable. 24. T, T, F, F, T Resistance to silver sulfadiazine is common for Enterobacter cloacae, S. aureus, and occasionally P. aeruginosa. All three of these organisms are usually sensitive to Mafenide. Silver nitrate can induce methemoglobinemia. Ideally surgical excision and closure of the wound should take place as soon as the child is stable enough for anesthesia. More than 105 organisms per gram of tissue constitute burn wound sepsis. Early surgical closure decreases significant blood loss. 26. E Thermal injury from smoke inhalation is usually limited to the supra-glottic airway. Inhalation injury accounts for more than 50% of the mortality associated with major burns. Carbon monoxide poisoning accounts for approximately 50% of the poisonings in the United States per year. The largest source of CO is generated from the incomplete combustion of carbon-containing compounds. 27. D The oxy-Hb dissociation curve is shifted to the left in CO poisoning, thereby enhancing oxygen affinity for Hb and impeding oxygen delivery from blood to tissue. The toxic effects of CO result from its direct action on the cytochrome-oxidase system and not solely on the reduced oxygen carrying capacity of the blood. If a significant amount of time has passed since the exposure of CO poisoning, an abnormal level may not be discovered. ( 28. D The heart rate and coronary blood flow increase in response to CO. Pulmonary edema occurs in about 10-30% of cases, however, the mechanism for pulmonary edema remains speculative. Cerebral blood flow and edema also increase. The cherry-red skin color is not commonly seen clinically. ( 29. T, F, F, T, T, T, T, T Muscle necrosis leads to myoglobinuria and subsequent acute renal failure. Salivary amylase is responsible for development of hyperamylasemia. A mild acidosis actually shifts the oxy-Hb dissociation curve to the right, increasing release of oxygen to the tissues and so should not be treated. The half-life of CO is 5-6 hours in room air, 1.5 hours in 100% FiO2, and less than 30 minutes in 100% FiO2 in 2.5 atmospheres. Hyperbaric oxygen treatment should be instituted when a patient has a CO Hb of more than 25%, signs and symptoms of CO poisoning, and a hyperbaric oxygen facility available. 32. D At low voltages, alternating current is more dangerous than direct current because of its ability to freeze the extremity to the electrical source. Joule's law states that power equals amperage squared times resistance (P = I 2 R). Surface burns result from the ignition of clothing or from the heat of the current traveling close to the skin. Arc burns are produced by a current that travels external to the body, as an electric arc forms between two objects of opposite charges. 

A CO 2 autoregulation is better maintained than blood pressure autoregulation.

35. D When using uncrossmatched blood, it is best to obtain at least an ABO and Rh type and partial crossmatch. This is sometimes referred to as an incomplete or partial crossmatch. The immediate phase crossmatch eliminates serious hemolytic reactions because of errors in the ABO typing. It will fail to detect only a few unexpected antibodies outside of the ABO system, most of which are clinically insignificant. If time does not permit even a preliminary screen, ABO and Rh type-specific, uncrossmatched blood is still preferable (and more abundant). Of patients never exposed to blood, fewer than 1 in 1000 will have an unexpected antibody detected in the immediate phase crossmatch. 36. E FFP provides the equivalent clotting factors of a single unit of fresh whole blood. The administration of FFP should be considered when 200% of the calculated circulating blood volume has been replaced with crystalloids and red cell concentrates. A precipitous fall in platelet count may not be tolerated, as well as a slow decline in thrombocytopenic patients. Platelet administration begins when 100-150% of the calculated circulating blood volume has been replaced with crystalloid and red cell concentrates. The dilutional coagulopathy is rapidly corrected once perfusion is restored, but may be exacerbated by the development or persistence of hypotension. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; p. 1483.) 37. C Bleeding and edema within an intact fascial compartment can lead to the development of increased pressure, muscle ischemia, and death. Whereas pulses may be intact distally with a compartment syndrome, one constant finding is severe pain even with passive motion. Muscle compartment pressures can be evaluated during the secondary survey of the trauma patient using an 18-gage needle and water manometer. Compartment pressures of 40 cm H 2 O should cause concern, whereas pressures greater than 60 cm H 2 O require fasciotomy. 39. D Almost all deaths from thoracic injury in children occur after the victim reaches the resuscitation center, and most children can be treated successfully with prompt diagnosis and aggressive early management. Penetrating injuries to the chest are unusual in children and usually result from fractured ribs rather than from external missiles. The mediastinum of the child is more mobile and this contributes to a low incidence of major vessel and airway injury. However, serious intrathoracic injury may be present in the absence of obvious chest wall injury. ( 41. D Flail chest injuries are rarely seen in children because high-velocity direct-chest trauma is uncommon. Additionally, rib fractures are less common in children than adults because children have very pliable ribs that are resistant to fracture. Contusions and/or penetrating injury of the lung parenchyma are frequently involved. The initial therapy should include humidified oxygen and a limitation of crystalloid resuscitation, if the remainder of the injuries permit, so that there will be a decrease in extravasation of fluid into the injured pulmonary parenchyma and a limitation of the secondary acute pulmonary edema. Definitive treatment of the flail chest takes place in the PICU by con- 

In the setting of pulmonary contusion, overhydration should be avoided because fluid will sequester in the damaged lung tissue and complicate the clinical condition. Radiographical evidence of a pulmonary contusion includes early consolidation of the lung parenchyma, which may be focal in nature, with resolution over 2-6 days. Empyema, or abscess formation, may occur after pulmonary contusion secondary to the extravasation of fluid and blood into the alveolar and interstitial spaces. 48. D Therapeutic hypothermia has not been shown to improve outcome. A body temperature of less than 32°C causes the cessation of shivering. Resuscitation of drowning victims should continue until the core temperature is at least 32°C. Pupillary dilatation occurs at a core temperature of less than 30°C. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition; pp. 882-889.)

Chest radiographs do not correlate with clinical outcome. Steroids have not been shown to be useful in improving the outcome for ischemic or anoxic insults. Intracranial pressure monitoring has not been shown to improve outcome in submersion injury. PEEP is often useful in treating the pulmonary dysfunction that is associated with a neardrowning episode, which is unresponsive to supplemental oxygen. The drowning victim will often swallow a large amount of water, which may induce emesis and subsequent aspiration. Consciousness is then lost. ( 

Stereotyped movement of the extremities and extensor posturing can be seen in patients who are clearly brain dead; these have been termed the Lazarus sign. Spinal and deep tendon reflexes are found on physical examination in at least 50% of brain dead patients. 2. D The power of a study is equal to 1 -β-error, which was set in this study at 0.2, and therefore the power of this study would be 0.8 or 80%. The P-value of this study was set at 0.05, and there is only a 20% chance that the authors actually missed an improvement owing to the new drug. There is an 80% chance that an improvement from the new drug was not missed. ( 11. C Parametric methods of statistical analysis use distribution assumptions (i.e., normal distribution) of data, and the distribution is described by mean and standard deviation. Nonparametric methods are also called distribution-free. These methods are based on analysis of ranks rather than actual data, and therefore, they are sometimes called rank methods. Skewed data are commonly analyzed by nonparametric methods. Methods using ranks are especially suitable for data, which are scores rather than measurements. Examples include apgar scores and stages of disease. 

Pediatric Critical Care

D It does not assume that the patient or the surrogate is competent. This must be assessed by the physician, as indicated in answer E. (Fuhrman BP, et al. Pediatric Critical Care

A It does include the ability to manipulate the information and deliberate about alternatives

D The best course of action is direct inquiry into their fears and guilt, which is likely to provide the best resolution for all parties. (Fuhrman BP, et al. Pediatric Critical Care

As long as the reason and the date are stated, adding to medical records is not illegal. Jurisdictions vary on the essence of compliance

D Accidents and adverse effects are the most common causes of death in children 13-15 years of age

regulations (introduced in 1982 by the Federal government) prohibit withholding or withdrawing of beneficial medical treatment from any infant on the basis of handicap or prognosis for quality of life. The three exceptions are: (1) infant is permanently comatose; (2) treatment is inhumane; and (3) infant is immediately dying