e206 SECTION XV Pediatric Critical Care Board Review Questions Rationale Reversal of neuromuscular blockade is possible only with nonde polarizing NMBAs The drugs used to reverse neuromuscular blockad[.]
e206 S E C T I O N XV Pediatric Critical Care: Board Review Questions Rationale Reversal of neuromuscular blockade is possible only with nondepolarizing NMBAs The drugs used to reverse neuromuscular blockade inhibit the enzyme acetylcholinesterase More acetylcholine is therefore available to compete with the NMBA at the nicotinic receptor of the neuromuscular junction The commonly used acetylcholinesterase inhibitors or “reversal agents” include neostigmine, pyridostigmine, and edrophonium Despite a similar mechanism of action, the clinical effects (such as onset and duration) of these agents differ Neostigmine and pyridostigmine are hydrolyzed by acetylcholinesterase During this process, the enzyme is carbamylated and inactivated Edrophonium does not break down the enzyme acetylcholinesterase; rather, it competitively and reversibly inhibits its function Sugammadex is a cyclodextrin, and instead of inhibiting the enzyme acetylcholinesterase, it forms a tight 1 : 1 complex with the steroidal neuromuscular blocking agents It has been shown to rapidly and effectively reverse rocuronium, vecuronium, and perhaps even pancuronium Because of a limited dissociation rate, the reversal is maintained Unlike the use of acetylcholinesterase inhibitors, reversal using sugammadex is feasible even with intense blockade, thereby providing the potential for the rapid reversal of neuromuscular blockade in the “cannot intubate—cannot ventilate” scenario Future studies are needed to fully evaluate this medication in the pediatric population Which of the following neuromuscular blocking agents causes initial bradycardia and hypotension, followed by tachycardia and hypertension? A Atracurium B Pancuronium C Succinylcholine D Vecuronium Preferred response: C Rationale Succinylcholine can have profound cardiovascular effects Typically, intravenous succinylcholine produces initial bradycardia and hypotension, followed after 15 to 30 seconds by tachycardia and hypertension With respect to use of succinylcholine in infants and children and in adults, which of the following statements is true? A Children have a slower clearance of succinylcholine compared with adults B Hyperkalemia resulting from succinylcholine administration is more common in adults compared with children C Neonates and infants require higher doses of succinylcholine on the basis of weight than older children and adults to produce apnea D Myoglobinemia from succinylcholine administration is more common in adults compared with children Preferred response: C Rationale Succinylcholine is a rapid-acting depolarizing muscle relaxant of ultrashort duration Succinylcholine is metabolized by butyrylcholinesterase Markedly prolonged neuromuscular blockade can result from atypical or abnormally low enzyme concentrations When differences in volume of distribution and concentration of anesthesia are taken into account, infants and small children appear relatively resistant to succinylcholine, have faster clearance, and have a shorter onset time (at equal multiples of ED95—the mean dose that produces a maximal effect of 95% twitch suppression for a given drug) Neonates and infants require about twice as much succinylcholine on the basis of weight than older children or adults to depress respiration or neuromuscular transmission or to produce apnea Adverse effects of succinylcholine include dysrhythmias, increased intraocular pressure, prolonged apnea, injured muscle membranes with associated hyperkalemia, association with masseter spasm, and malignant hyperthermia and death Infants and small children have a high incidence of such complications In infants and small children, profound sustained sinus bradycardia (50 to 60 beats/minute) is frequently observed; rarely, asystole occurs Because of limited muscle mass, the infant or small child, in contrast to the adult, seldom has strong fasciculations with the use of succinylcholine In healthy patients, succinylcholine increases plasma levels of potassium by 0.3 to 0.5 mEq/L Alarming concentrations of potassium, as high as 11 mEq/L, along with cardiovascular collapse, have been frequently reported with succinylcholine in a variety of conditions, including burns, massive trauma, stroke, spinal cord injury, and muscle disease Strong fasciculations are not necessary to produce hyperkalemia in susceptible patients No data exist to suggest that the infant is any less vulnerable than the adult to massive potassium flux from the listed conditions A high incidence of myoglobinemia occurs after the administration of succinylcholine in prepubertal patients, especially those anesthetized with halothane Myoglobinemia rarely results from succinylcholine administration in adults CHAPTER 136 Board Review Questions e207 Chapter 132: Sedation and Analgesia A 15-year-old girl with history of severe persistent asthma is admitted to the Pediatric Intensive Care Unit (PICU) with acute respiratory failure secondary to near-fatal asthma Patient was receiving continuous albuterol nebulization at 20 mg/h in addition to intravenous terbutaline at mg/kg/ and placed on bilevel positive airway pressure (BiPAP) for further respiratory support Six hours later, patient was intubated due to worsening respiratory status, increased work of breathing, and worsening respiratory acidosis and hypercapnia Patient was placed on mechanical ventilation on synchronized intermittent mandatory ventilation (SIMV) pressureregulated volume control (PRVC) mode with a positive end expiratory pressure (PEEP) of cm H2O, tidal volume (TV) of 10 mL/kg, intermittent mandatory rate of breaths per minute with inspiratory time of second and expiratory time of seconds Inhalational anesthetic gas isoflurane was started and maintained at 2% Other bronchodilator therapies were stopped Patient began to improve clinically with resolution of hypercapnia The most recent arterial blood gas (ABG) revealed pH 7.31 and Paco2 56 torr Six hours later, patient developed fever of 40C which did not respond to acetaminophen and ibuprofen via nasogastric tube, and rapid increase in Paco2 to 98 torr The patient’s lung examination remains unchanged and chest radiograph reveals hyperinflation and absence of pneumothorax What is the most appropriate next step in the management of this child? A Adjust ventilator settings to increase TV and lower ventilator rate B Give acetaminophen IV and repeat ABG in 30 minutes C Obtain blood and tracheal culture and start broad spectrum antibiotics D Perform bronchoscopy to clear mucus plugs E Stop isoflurane, aggressive body cooling, and start dantrolene immediately Preferred response: E Rationale This represents a case of malignant hyperthermia (MH) secondary to isoflurane use Isoflurane is an inhalational anesthetic gas that has been used in the PICU for patients with near-fatal asthma due to its bronchodilatory effects MH is a rare reaction that may occur whenever inhalational anesthetics or succinylcholine are used It involves the unrestrained entry of calcium into myocytes and consequential consumption of adenosine triphosphate, resulting in metabolic failure Hypermetabolism, manifested by increased CO2 production, and acidosis occur The body temperature rises and death from hyperkalemia ensues Immediate discontinuation of isoflurane, correction of electrolyte abnormalities, aggressive cooling, and the administration of dantrolene are urgently indicated Pediatric intensivists should be vigilant of this rare complication even hours after initiation The rise in Paco2 in this case should not be assumed to be the result of mucus plugging or hypoventilation until MH is ruled out MH is a true emergency and time is of the essence, so administering acetaminophen and waiting to repeat ABG could be detrimental Fever in this case could be caused by infection, so starting IV antibiotics is not unreasonable, but this should be initiated only after ruling out MH 2 A previously healthy 2-year-old boy was admitted to the pediatric intensive care unit with acute respiratory failure secondary to respiratory syncytial virus (RSV) bronchiolitis Patient was intubated and placed on mechanical ventilation Fentanyl intravenous infusion at mg/kg/h and dexmedetomidine at mg/kg/h were started for analgesia and sedation Patient remained comfortable while receiving the current regimen but developed urinary retention necessitating insertion of an indwelling catheter On examination, pupils were constricted at mm bilaterally and reactive to light Heart rate was 110 beats per minute, blood pressure was 95/52 mm Hg, he was breathing at 25 breaths per minute similar to the intermittent mandatory rate set on the mechanical ventilator In this patient, the therapeutic effects of analgesia, respiratory depression, and pupillary constrictions are mostly attributed to: A Agonist activity at delta (d) receptors B Antagonist activity at mu (µ) receptors C Agonist activity at mu (µ) receptors D Agonist activity at GABA type A (GABAA) receptor Preferred response: C Rationale Opioids (e.g., fentanyl) are agonists at various opioid receptors, for which several endogenous ligands exist There are three major classes of receptors: mu (µ), kappa (k), and delta (d) Opioid receptors possess the same general structure: an extracellular N-terminal region, seven transmembrane domains, and an intracellular C-terminal tail structure Subtypes of each receptor (e.g., µ1, µ2) exist, as less well-characterized opioid receptors such as nociceptin Fentanyl is a potent µ-agonist and is 100 times more potent than morphine Most of the therapeutic and adverse effects can be accounted for by agonist activity at the µ-receptor, which is responsible for analgesia, respiratory depression, pupillary constriction, and euphoria At the cellular level, µ-receptor activation through a coupled G protein inhibits adenylate cyclase, resulting in inhibition of voltage gated calcium entry channels and activation of potassium channels This results in a loss of K1 from the neuron causing hyperpolarization and depression of excitability in the nervous system Associated effects on cholinergic, adrenergic, serotonergic, and dopaminergic neurotransmitter systems are seen within the central nervous system These receptors are found at multiple sites along pain pathways including the spinal cord, midbrain, thalamus, and cortex Benzodiazepines are among the most commonly used agents for sedation in the ICU They augment the function of the GABA type A (GABAA) receptor at the postsynaptic membrane e208 S E C T I O N XV Pediatric Critical Care: Board Review Questions A previously healthy 5-year-old girl is admitted to the pediatric intensive care unit with acute respiratory failure secondary to rhinovirus bronchiolitis with superimposed right lower lobe bacterial pneumonia She is requiring high flow nasal cannula (HFNC) at mL/kg/min and fraction of inspired oxygen (Fio2) of 0.55 The decision was made to escalate support and apply noninvasive ventilation using bilevel positive airway pressure (BiPAP) device using a face interface (mask) She became more agitated soon after application, voicing her desire to remove the mask because it was bothering her Her respiratory status began to improve, but she is still in need of BiPAP support Given the circumstances, what is the most appropriate next step in the management: A Dexmedetomidine intravenous infusion at 0.2 mg/kg/h B Fentanyl intravenous infusion at mg/kg/h C Midazolam intravenous infusion at 0.1 mg/kg/h D Morphine 0.1 mg/kg intravenously every hour E Propofol intravenous dose of mg/kg that can be repeated every few minutes as needed Preferred response: A Rationale Dexmedetomidine is commonly used as a single sedative agent in patients receiving noninvasive mechanical ventilation and considered to be the medication of choice during these clinical scenarios Dexmedetomidine is a selective a2-adrenergic agonist It acts centrally in the locus ceruleus (sedation), in the spinal cord (analgesia), and in autonomic ganglia Stimulation of the a2 receptor decreases the release of norepinephrine, inhibits sympathetic activity, and produces sedation, anxiolysis, and analgesia The recommended dosage for dexmedetomidine is intravenous infusion of 0.2 to 0.7 mg/kg/h It appears that in pediatric patients, a higher end of the dose range is required Doses higher than 1.5 µg/kg/h have not been shown to provide any further sedative action Advantages of dexmedetomidine include minimal respiratory depression and predictable hemodynamic effects Because of the reduced sympathetic activity, blood pressure and heart rate fall slightly Narcotics (e.g., fentanyl and morphine) can cause respiratory depression as a result of the agonist activity at the µ-receptor Midazolam is a water-soluble benzodiazepine with short half-life that has central nervous system depressant effects and can cause respiratory depression as well Propofol is a rapid-acting intravenous anesthetic agent, is considered a potent respiratory depressant, and should not be used as a possible sedative in patients with acute respiratory failure receiving noninvasive ventilation Which of the following opioids has the risk of excessive effect due to genetic based ultra-rapid metabolism A Codeine B Fentanyl C Meperidine D Morphine E Remifentanil Preferred response: A Rationale Some patients are ultra-rapid deacetylators of codeine which results in a more rapid and higher concentration of morphine This has been associated with significant respiratory depression in the postoperative period of some children with obstructive sleep apnea associated with tonsillar hypertrophy 5 Which of the following is not a component of the Withdrawal Assessment Tool-1 (WAT-1): A Agitation B Loose Stools C Sweating D Tachycardia E Tremor Preferred response: D Rationale The signs and symptoms of opiate and benzodiazepine withdrawal are in many cases nonspecific There are often many other reasons for these signs and symptoms in the critically ill pediatric patient Signs of sympathetic hyperactivity, although associated with withdrawal phenomena, may not be predictive of an abstinence syndrome However, the Sophia Observational Score (SOS) does include tachycardia as one of the features Which of the following statements is not correct with respect to the use of dexmedetomidine in pediatric sedation? A a2 receptor selectivity compared to the a1 receptor B Less risk of respiratory depression compared to routinely used other ICU sedatives C Lower risk of postsedation delirium compared to routinely used other ICU sedatives D Some analgesic effect E There is little risk of a withdrawal syndrome Preferred response: E Rationale Dexmedetomidine has proven useful as an adjunct to manage withdrawal from opiates and inhalational agents However, the prolonged use of dexmedetomidine has been associated with a withdrawal syndrome that is often associated with sympathetic overactivity Although it has been less well studied than for opiates and benzodiazepine, clonidine may be useful in its prevention or treatment Which of the following opiates is metabolized to a more toxic drug? A Codeine B Fentanyl C Meperidine D Remifentanil Preferred response: C Rationale Meperidine is metabolized by the liver to normeperidine, which is twice as toxic as meperidine and has a longer half-life (T½, 15 hours) Normeperidine accumulation is enhanced in patients with an induced cytochrome P-450 system Which of the following drugs is the most potent opioid in clinical practice? A Alfentanil B Fentanyl C Hydromorphone D Sufentanil Preferred response: D CHAPTER 136 Board Review Questions e209 Rationale Hydromorphone is seven times as potent as morphine Morphine is 100 times less potent than fentanyl Sufentanil is to 10 times more potent than fentanyl and is the most potent opioid in clinical practice, posing a high risk of apnea with bolus administration Alfentanil is five times less potent than fentanyl Which of the following opioids has the shortest elimination half-life? A Fentanyl B Meperidine C Morphine D Remifentanil Preferred response: D Rationale The half-lives of the aforementioned opioids are as follows: alfentanil, 90 minutes; fentanyl, hours; morphine, hours (longer in younger children); meperidine, 15 hours; and remifentanil, minutes 10 Which of the following opioids does not require a bolus dosing to achieve a rapid change in effect when given as a continuous infusion? A Alfentanil B Fentanyl C Morphine D Remifentanil Preferred response: D Rationale Sedation with remifentanil can be effectively managed by continuous infusion without the need for a bolus because of the short T½ An increase or decrease of infusion rate is rapidly reflected by a change in the degree of sedation, which is important to note Most other opiate sedatives require bolus dosing to achieve a rapid change in effect Bolus dosing is neither appropriate nor needed for remifentanil 11 Compared with morphine, which of the following statements is true about methadone? A It has inactive metabolites B It is an ineffective analgesic C It is more sedating D It is more potent Preferred response: A Rationale Methadone has an oral bioavailability of 80% to 90% and an elimination half-life of 12 to 24 hours It is equipotent to morphine Methadone has inactive metabolites and is less sedating than morphine while remaining an effective analgesic Because of its higher bioavailability and reduced first-pass metabolism, it is more predictable orally than is morphine It has been extensively used in the outpatient management of patients addicted to opiates 12 Which of the following opiate receptors is responsible for the respiratory depression seen with morphine? A delta (d) B kappa (k) C mu1 (µ1) D mu2 (µ2) Preferred response: D Rationale Opioids are agonists at various opioid receptors, for which several endogenous ligands exist Three major classes of receptors exist: mu (µ), kappa (k), and delta (d) The opioid receptors possess the same general structure of an extracellular N-terminal region, seven transmembrane domains, and an intracellular C-terminal tail structure Subtypes of each receptor (e.g., µ1, µ2) exist, as less well-characterized opioid receptors d, k, and s Most of the therapeutic and adverse effects can be accounted for by agonist activity at the µ receptor, which is responsible for analgesia, respiratory depression, pupillary constriction, and euphoria 13 Which of the following opiates has an active metabolite with a higher potency than the agonist itself? A Codeine B Fentanyl C Meperidine D Morphine Preferred response: D Rationale Morphine is metabolized to morphine-3-glucuronide (M3G) and M6G in the liver M3G is the major metabolite and has little morphine-like activity, although some research has suggested that M3G may be associated with an antinociceptive effect, accounting for failure of analgesia during long-term use In contrast, M6G is many times more potent than morphine itself Morphine undergoes significant first-pass hepatic metabolism, whereby after a single parenteral dose, only morphine is initially active After a single dose by mouth, both morphine and M6G are active With long-term oral use, M6G accumulates until its analgesic effect is greater than that of morphine A similar effect can be anticipated with long-term morphine infusion in the patient in the pediatric ICU (PICU) 14 Which of the following options displays the correct order of potency, from most to least potent? A Fentanyl sufentanil morphine meperidine B Fentanyl morphine meperidine sufentanil C Morphine meperidine fentanyl sufentanil D Sufentanil fentanyl morphine meperidine Preferred response: D Rationale Sufentanil is to 10 times more potent than fentanyl and is the most potent opioid used in clinical practice Fentanyl is 100 times more potent than morphine Meperidine has one-tenth the potency of morphine e210 S E C T I O N XV Pediatric Critical Care: Board Review Questions 15 Compared with fentanyl, alfentanil has which of the following? A Higher potency B Longer elimination T½ C More prolonged onset of action D Shorter duration of action Preferred response: D Rationale Alfentanil is times less potent than fentanyl Although it is less lipid soluble than fentanyl because of its low pKa (negative logarithm of the acid ionization constant), a higher percentage of the drug is present in the active un-ionized form, which results in a rapid onset Because of its low volume of distribution, alfentanil has a short elimination half-life, which results in a short duration of action (5 to 10 minutes) 16 Which of the following sedatives is known to have negative inotropy and chronotropy properties in critically ill patients? A Diazepam B Fentanyl C Lorazepam D Midazolam Preferred response: D Rationale Benzodiazepines (BZDs) have few cardiovascular adverse effects, but in a sick, intensive care population, profound cardiovascular depression may occasionally be observed BZDs should be used judiciously until the patient response is known Midazolam has been most often associated with this effect, and research in dogs has shown both negative inotropy and chronotropy, especially when the sympathetic response has been abolished 17 Which of the following statements regarding T½ benzodiazepines is correct? A Midazolam has a longer elimination half-life than lorazepam B The elimination of lorazepam is 14 hours C Lorazepam is metabolized by the cytochrome P-450 system D Midazolam toxicity is related to propylene glycol Preferred response: B Rationale Diazepam is highly lipid soluble with a long T½ (24 hours) Metabolism by oxidative biotransformation generates several hypnotically active metabolites with an elimination T½ that may be longer than diazepam including oxazepam (T½, 10 hours) and N-dimethyldiazepam (T½, 93 hours) Lorazepam produces sedation for to hours after a single dose It has a slower onset than midazolam The elimination T½ is about 14 hours Metabolism is by glucuronyl transferase, not the cytochrome P-450, and there are no active metabolites Lorazepam for intravenous use has propylene glycol as a carrier There is a risk of a metabolic lactic acidosis because of the metabolism of this carrier Cases of fatal metabolic acidosis from propylene glycol have been reported in neonates taking a particular vitamin preparation Midazolam has a short elimination T½ of hours In which situation is use of flumazenil contraindicated? A Recovery from conscious sedation with midazolam B Respiratory depression with use of benzodiazepine C Treatment of paradoxical reaction to midazolam D Tricyclic antidepressant overdose Preferred response: D Rationale Flumazenil is indicated for the complete or partial reversal of the central sedative effects of benzodiazepines (BZDs) Contraindications include patients who have a known hypersensitivity to BZDs, patients with epilepsy who are receiving BZD treatment, and those who have overdosed with a tricyclic antidepressant The use of flumazenil is often associated with mild to moderate tachycardia and hypertension In cases of multiple drug overdose, the use of flumazenil remains controversial It is often overused in the emergency setting without due concern for potential adverse reactions because of the potential toxic effects (cardiac arrhythmias or convulsions) of other psychotropic drugs ingested The toxicity of tricyclic antidepressants becomes apparent as the effects of BZDs are antagonized Patients should be evaluated for the signs and symptoms of a tricyclic antidepressant overdose, and an electrocardiogram may be helpful in determining the risks involved Which of the following is an adverse effect of haloperidol? A Bradycardia B Extrapyramidal signs C Hypotension D Vomiting Preferred response: B Rationale Haloperidol is a potent antipsychotic agent with a nonspecific dopamine antagonist action It has little effect on the cardiovascular or respiratory systems It produces the appearance of calm with minimal hypnotic effect and reduces operant behavior (purposeful movement) The patient appears tranquil and dissociated from his or her surroundings but is readily accessible if spoken to Haloperidol may mask actual feelings of mental restlessness It is a potent antiemetic agent (with action at the chemotrigger zone) and has no appreciable effect on the electroencephalogram It potentiates analgesics and other sedative agents Compared with less potent butyrophenones, it has fewer adverse effects Neuroleptanalgesia, a dissociative form of anesthesia, can be induced when haloperidol is combined with high-dose opiates This anesthetic state is useful for certain cardiac and neurosurgical procedures that require cardiovascular stability and a responsive patient It is metabolized to inactive compounds with a T½ of 15 to 25 hours It is highly protein bound Hepatic dysfunction increases the T½ because of reduced clearance Adverse effects include extrapyramidal signs, although acute dystonia is rare Prolongation of the QT interval is possible with the subsequent risk of ventricular tachycardia Hepatic toxicity can occur but is rare 20 Which of the following inhalational agents is most widely used in ICUs because of its safety profile? A Desflurane B Enflurane C Halothane D Isoflurane Preferred response: D ... urgently indicated Pediatric intensivists should be vigilant of this rare complication even hours after initiation The rise in Paco2 in this case should not be assumed to be the result of mucus plugging... waiting to repeat ABG could be detrimental Fever in this case could be caused by infection, so starting IV antibiotics is not unreasonable, but this should be initiated only after ruling out MH... blood pressure was 95/52 mm Hg, he was breathing at 25 breaths per minute similar to the intermittent mandatory rate set on the mechanical ventilator In this patient, the therapeutic effects of