Pediatric Examination and Board Review (25 page)

(A) “crack”

(B) OxyContin

(C) ecstasy

(D) cannabis

(E) ketamine

7.
Before his deterioration in the recovery room, the child received an anesthetic with isoflurane, nitrous oxide, cisatracurium, and meperidine to have teeth removed. With the drug screen positive for amphetamines, the following must be considered in the differential diagnosis

(A) seizures and a postictal state

(B) neuroleptic malignant syndrome

(C) central serotonin syndrome

(D) all of the above

(E) none of the above

8.
The increased synaptic release of serotonin can be as a result of which drug in this case scenario

(A) meperidine

(B) nitrous oxide

(C) methamphetamine

(D) lorazepam

(E) succinylcholine

9.
The other agent in this clinical condition that affects serotonin pharmacology is

(A) isoflurane

(B) cisatracurium

(C) phenelzine

(D) lorazepam

(E) fentanyl

10.
In the case of neuroleptic malignant syndrome (NMS), the neurotransmitter implicated is

(A) epinephrine

(B) norepinephrine

(C) serotonin

(D) dopamine

(E) GABA

11.
The symptoms that are more common in the NMS than in the central serotonin syndrome include all of the following except

(A) hyperthermia

(B) altered mental status

(C) muscle rigidity

(D) myoclonus

(E) none of the above

12.
Drugs implicated in the central serotonin syndrome include the following except

(A) dextromethorphan

(B) MAO inhibitors

(C) selective serotonin reuptake inhibitors (SSRIs)

(D) acetaminophen with codeine

(E) lithium

13.
The mortality of the central serotonin syndrome (CSS) is

(A) less than 20%

(B) 20-40%

(C) 40-50%

(D) 50-75%

(E) more than 75%

14.
Treatment of CSS includes the following except

(A) cyproheptadine

(B) propranolol

(C) mannitol

(D) phenoxybenzamine

(E) none of the above

15.
In NMS, treatment includes the following except

(A) bromocriptine

(B) dantrolene

(C) chlorpromazine

(D) mannitol

(E) antipyretics

ANSWERS

1.
(A)
Hyperthermia is defined as an elevation of core body temperature above 37.5°C. In contrast to fever, which is a cytokine-activated inflammatory response, hyperthermia is a failure of thermoregulation. Obviously, in the child who presents with an elevated temperature, it is frequently not clear whether you are dealing with an inflammatory fever or with a hyperthermic state. Given the absence of a history of inflammatory or clinical features of an infectious disease of any kind, the child described in the case scenario should be presumed to have a hyperthermic state related to one of the medications he received during his medical care or, perhaps, to a medication he ingested himself. In the case described, the appropriate initial interventions as always are the ABCs of urgent care. The patient needs a patent airway, adequate respirations, and hemodynamic stability. After stabilization, a number of laboratory tests may provide helpful information including an ECG. In all the hyperthermic states, it is likely that the patient will have a mixed acidosis. Elevation of muscle enzymes significant enough to cause renal insufficiency, and increased serum concentrations of both potassium and phosphate are also likely present. These aberrations are largely the result of muscle membrane injury, the subsequent release of intracellular contents, and the hemodynamic challenge of significant hyperthermia. Emergency treatment must focus on the distinct possibility of life-threatening dysrhythmias from acidosis and hyperkalemia.

2.
(C)
When there is an acute change in PCO
₂
of 10, the pH will change by 0.08 in the opposite direction. In other words, the pH will fall as the PCO
₂
rises. The acidosis or alkalosis present is purely respiratory if all changes are explained by changes in the PCO
₂
. For a change in BE of 10 mEq/L, the pH will change by 0.15 in the same direction. If all changes are explained by a change in the BE, then the process is entirely metabolic.

Assuming a normal blood gas of 7.40, PCO
₂
40, PO
₂
100, BE 0, in the case presented, the PCO
₂
is approximately 35 above the normal PCO
₂
. Divided by 10 and multiplied by 0.08, one would expect the pH to be 0.28 lower than the normal of 7.40, or 7.12. In this case, the pH is 7.07 with a base deficit of −10 and a metabolic acidosis is also present.

3.
(D)
Given the proximity of this event to a general anesthetic, the first cause of hyperthermia to be considered is malignant hyperthermia (MH). Early clinical findings in MH include masseter muscle spasms, generalized muscle rigidity, sinus tachycardia, increase in CO
₂
production leading to hypercarbia, and elevation in body temperature. Hemodynamic instability, electrolyte abnormalities, and disseminated intravascular coagulation occur later. Appropriately treated, MH has a mortality that is less than 5% (
Table 12-1
).

4.
(D)
Appropriate intervention in a patient with suspected or proven MH is immediate cessation of the ongoing anesthetic, aggressive external and internal cooling, and the IV administration of dantrolene. Dantrolene is a drug that interferes with calcium release from the sarcoplasmic reticulum and will put an end to the metabolic abnormality. Because rhabdomyolysis, which may result in acute renal failure, is very common in this disorder, treatment with hydration, bicarbonate to alkalinize the urine followed by diuresis induced by mannitol is also recommended. After a dose(s) of dantrolene is/are given, the treatment of MH is supportive.

5.
(A)
MH is a rare genetic disorder associated with the administration of a variety of anesthetic agents, particularly the depolarizing muscle relaxant succinylcholine and volatile anesthetic gases. In approximately half of the identified cases, MH is inherited in an autosomal dominant fashion. In the remainder of the cases, inheritance is variable. When exposed to a triggering anesthetic, susceptible patients have the uncontrolled release of calcium from their sarcoplasmic reticulum. This torrential release of calcium results in a marked increase in skeletal muscle metabolism and heat production.

Once the episode has resolved and the patient has recovered, it is suggested that the patient and his first-degree relatives be evaluated for this diagnosis. The diagnosis requires a muscle biopsy, which should be done at a certified MH center. Abnormal augmentation of muscle contraction following treatment of the biopsy specimen with halothane or caffeine is diagnostic. A variety of MH centers are located across the country and can be accessed by calling the Malignant Hyperthermia Hotline (1-800-MH-HYPER/644-9737).

6.
(C)
In the development of this case scenario, it becomes apparent that this child has a drug screen that is positive for amphetamines. The commonly used street drug responsible for this is ecstasy. Ecstasy is a methamphetamine derivative that significantly impacts the physiology of the human nervous system by alterations in serotonin metabolism.

7.
(D)
Important causes of severe hyperthermia (>40°C temperature), not related to infectious diseases, are environmental exposure, hypothalamic injury, central serotonin syndrome, MH, and neuroleptic malignant syndrome (
Table 12-1
). The clinical symptoms associated with these syndromes overlap significantly. Each of these conditions can be associated with multisystem complications, and each can result in death. For CSS to be diagnosed, there needs to be an appropriate history of ingestion of medication that contributes to an increase in serotonin in the CNS. Additionally, the patient must have at least 3 of the following: mental status changes, agitation, myoclonus, muscle rigidity, hyperreflexia, diaphoresis, shivering or tremor, diarrhea, incoordination, and fever.

TABLE 12-1.
Contrasting Clinical Features of Syndromes Associated with Severe Hyperthermia