Outline
1. Apnea of Prematurity (AOP)
Apnea occurrence is common in premature infants. The lower the weight
and gestational age at birth, the higher the incidence:
< 30 weeks GA 80%
30 - 31 weeks GA 50%
32 - 33 weeks GA 14%
34 - 35 weeks GA 7%
If off ventilatory support, in 77% of the infants first episode occurs within
first 2 days of life. Almost all occur within the first week of life.
Recurrence of events is common and for how long depends on gestational age
at delivery:
Immaturity is a major underlying factor, however apnea can be initial
(or only) manifestation of multiple other problems, and AOP should be exclusion
diagnosis if no other problem identified:
| CNS | Systemic | Metabolic | Thermal | Anatomical |
| IVH | Sepsis | Hypoglycemia | Hyperthermia | Choanal atresia |
| Seizures | Shock (hypovol.) | Hyponatremia | Hypothermia | Micrognathia |
| Hydrocephalus | Heart failure | Hypocalcemia | Macroglossia | |
| Drug depression | Acidosis | Inborn errors | Tracheomalacia | |
| Malformations |
Polysomnogram: Most of apneas are of mixed type, specially if they are
prolonged. Usually central component at start of event, then obstructive
component follows. Purely obstructive apneas not common, unless airway anatomical
problem also present. Increased periodic breathing times is also characteristic.
Management: In absence of any underlying problems, these are some
helpful guidelines
a) Infants born at <35 weeks of GA (and not on ventilatory support) should
be monitored for the first week of life, at least.
b) Infants with less than 10 apneic episodes a day, without profound hypoxemia
or bradycardia and with quick response to stimulation should be simply watched.
c) Infants with several episodes during the day, with prolonged episodes
associated with hypoxemia and/or bradycardia, with slow response to stimulation,
requiring bag-and-mask ventilation to recover, should go through a trial
of xanthines (caffeine, theophylline).
d) Infants who fail to xanthines could be tried on CPAP. IV Doxapram infusion
has been advocated by some, with variable success.
e) Infants with refractory apnea and severe episodes should be considered
for long term, low-setting mechanical ventilation.
Home monitoring: hot issue. Most advocate continued monitoring until 1 week
after attaining term post-conceptual age.
2. Acute Life Threatening Episode (ALTE)
Best defined as an acute and unexpected episode that is frightening
to the parent (or observer) and that brings infant to medical attention.
Term was coined to replace 'near-miss SIDS' which inaccurately implies association
with SIDS. Term should be understood as merely a syndrome that describes
chief complain at presentation for many possible different entities.
Incidence, prevalence pretty much unknown, this mostly due to inconsistencies
in definitions, inconsistencies in diagnostic efforts, heterogeneity of
possible causes, etc. Usually occurs in infants with young mothers, of low
socioeconomic status. Most episodes occur during daytime hours and when
infant is awake.
When no etiology is identified after exhaustive investigation (usually
this happens in 1/3 of the cases), then infant should be diagnosed as Apnea
of Infancy (see below).
Typically one or a combination of the following at presentation: apnea,
color change, limpness, rigidity, posturing, vomiting, choking, abnormal
movements, crying, sweating, noisy breathing, coughing.
Conditions that can present as an ALTE:
| Digestive (47%) | Neurological (29%) | Respiratory (15%) |
| GER, aspiration | Vasovagal response | Infection (RSV, Pertussis) |
| Infection | Seizure disorder | Airway abnormality |
| Malformations | Infection | Alveolar hypoventilation |
| Dumping | Subdural hematoma | |
| Malformations |
| Cardiovascular (3.5%) | Metabolic (2.5%) | Miscellaneous (3%) |
| Cardiomyopathy | Hypoglycemia | Accidents |
| Infection | Hypocalcemia | Sepsis |
| Arrythmia | Food intolerance | Munchausen by proxy |
| CHD | Inborn errors | Drug effect |
Treatment and prognosis are contingent to etiology of episode. Thorough
history (interview all caregivers, consider scene inspection in doubtful
cases) and physical exam will help pinpoint problem and direct work up in
most cases.
Home monitoring: hot issue. No definite universally accepted criteria.
For most infants, if etiology of event well defined and under treatment,
no need for home monitoring. Frequently indicated for those infants that
required resuscitation, those with abnormal polysomnograms or those with
family history of two or more SIDS victims. When to stop?, no clearcut criteria,
most recommend discontinuation after 3 months of monitoring with no events
recorded.
Unexplained episode of apnea longer than 20 seconds associated with cyanosis,
pallor, bradycardia and(or) marked hypotonia. Episode in infant born at
>38 weeks GA. In a nutshell: ALTE that remains unexplained after
exhaustive investigation.
True incidence and prevalence figures not known, 1/3 of all ALTE's are
AOI's.
Autonomic dysregulation has been proposed as pathophysiologic mechanism,
evidence for both sympathetic and vagal abnormalities have been reported.
Profuse sweating, increased heart rate responses to different stimuli, and
minor or subtle difficulties during swallowing are among the most common
findings.
8 to 23% of those infants who have repeated episodes will subsequently
die of SIDS. Those who do not have repeated episodes are still at risk of
death from SIDS, 0 to 6% will subsequently die from SIDS. Those at higher
risk of death from SIDS are infants that had the initial apneic event during
sleep, that required resuscitation (CPR) to survive the event and
those with family history of SIDS deaths. (These group may truly represent
'near-miss SIDS' cases).
Polysomnogram findings are variable, but for most infants study will
be normal or with few mild abnormalities. Prolonged central apneas, hypopneas
or oxygen desaturations are found rarely.
Home monitoring is indicated for these infants. Role of central stimulants
is debatable, unless polysomnogram is abnormal. Recommendation is to continue
monitoring until at least 3 months free of events are observed. However,
it has not been proven that this intevention truly decreases the risk of
subsequent death from SIDS.
For most infants prognosis is good. Five years after initial episode
neurodevelopmental performance is similar to that of age matched peers.
Ten years after initial episode no differences in IQ or behavioral tests
are seen when compared to age matched controls.
4. Sudden Infant Death Syndrome (SIDS)
NIH consensus panel report, 1987: "sudden death of any infant or
young child, which is unexpected by history and unexplained by a thorough
post-mortem examination".
Incidence in US general population: 1.3 deaths per 1,000 live births.
Higher incidence in blacks (5.1 per 1,000) and Native-Americans (2.3 per
1,000).
Among recognized risk factors, family history of SIDS is the strongest
one. Siblings of SIDS victims are at 10 to 20 times higher risk than the
general population, if there was more than one SIDS death in the family
the risk is 180 times higher. A twin sibling of a SIDS victim has a 10 times
higher risk. Prenatal drug exposure (opiates, cocaine) is associated with
an increase in risk of 10 to 30 times. Other maternal factors such as age,
socioeconomic status, inadequate prenatal care, smoking, low weight gain
or anemia during pregnancy, prenatal infections (UTI's, STD's) have also
been found to be associated with SIDS.
Prone position during sleep has been found in multiple studies to be
associated with SIDS, with SIDS victims being 3 to 9 times more likely than
matched controls of having been put to sleep prone before death. Interventions
directed at changing sleep positioning practices conducted in Australia,
New Zealand, Britain and Scandinavia have all resulted in significant reductions
in the incidence of SIDS. Task force from the American Academy of Pediatrics
issued statement in 1992 recommending educational campaign to change sleep
positioning practices in the US.
Etiology of SIDS still unknown. Autopsy findings are very subtle and
do not help to explain death. Mild pulmonary edema and intrathoracic petechiae
are seen in around 80% of cases. More detailed studies will reveal in most
cases subtle findings compatible with prolonged hypoxia or prior asphyxia.
Hyperplasia of pulmonary arteriolar smooth muscle, retention of periadrenal
brown fat, heaptic erythropoeisis, hyperplasia of bone marrow red cell precursors,
and abnormal proliferation of brainstem astroglial fibers, among most commonly
reported.
Most compelling explanation is presence of one or more abnormalities in central (brainstem) cardiorespiratory control:
To date no reliable method to identify prospectively SIDS vistims has
been found. Large studies performing different forms of polysomnography
have failed to identify infants who subsequently died from SIDS. This may
be in part due to our incomplete understanding of SIDS pathophysiology.
However, there is a lack of studies focused on high risk groups.
Home monitoring has not been particularly helpful in decreasing the number
of SIDS victims. This in part could be due to the fact that respiratory
control abnormalities are not the only mechanism that leads to SIDS, but
it also reflects the problems related with the ease of use and compliance
with the systems currently in use. At least 50% of those infants that died
from SIDS while being 'monitored', were not using the monitor at the time
of death.
5. Obstructive Sleep Apnea Syndrome(OSAS)
Obstructive Sleep Apnea: Cessation of airflow associated with inspiratory
efforts that occurs during sleep (REM or Non-REM)and that results in significant
hypoxia and hypercarbia.
In children diagnosis of OSAS is based on the presence of 2 conditions:
OSA is the result of sleep-related pharyngeal airway obstruction. Maintenance
of the pharyngeal airway during sleep accomplished by a delicate balance
between the tone of the pharyngeal muscles (which tend to keep the airway
open) and the negative suction force generated by the diaphragm during inspiration.
The presence of an increased upper airway resistance contributes to the
suction force created by the diaphragm. Once collapse occurs, the apposition
of the airway mucosal surfaces creates an additional force that contibutes
to maintain the airway obstruction:
Incidence of OSAS in children is unknown, snoring is not uncommon in
children, but it not always results in OSAS. Data from small studies have
estimated incidence from 9% to 21%. Peak incidence in the 2 to 5 year old
group, possibly because of prominence of pharyngeal lymphoid tissue at that
age range.
Typical chief complain is loud snoring during sleep that persists throughout
the night. Episodes of apnea are frequently noticed by the parents and described
as loud and harsh snoring followed by complete silence for several seconds
and that is abruptly terminated by arousal, rapid breathing with mild snoring
or movement in bed. Excessive sweating, bedwetting, somnolence during the
day, mouth breathing, chronic rhinorrhea, recurrent ear or upper respiratory
infections, hyperactivity, difficulty to concentrate, school problems, are
also commonly reported by the family.
OSAS is usually the result of anatomical abnormalities, and can be the result of several entities. Among the most common ones:
| Adenotonsillar hypertrophy | Micrognathia |
| Choanal atresia | Macroglossia |
| Craniofacial abnormalities | Down's syndrome |
| Obesity | Allergic rhinits |
| Pharyngeal tumors | Nasal foreign body |
| Velopharyngeal flap | Deviated nasal septum |
| Chronic rhinitis | Static encephalopathy |
Usually a good HEENT exam will uncover any of these problems. Lateral airway radiograms with the neck extended will help confirm the diagnosis, upper airway fluoroscopy (more on if performed with the child sleeping) can give valuable information as to airway dynamics.
Sleeping or early morning blood gas will show significant elevation of Pco2, also blood gas will reveal chronic respiratory acidosis. EKG should be done in any child with OSAS to assess for severity of problem, as represented by changes compatible with any degree of pulmonary hypertension.
Polysomnogram will show typical obstructive events with desaturations. Polysomnogram can be performed at home, but for some clear cut cases just having parents tape record child during sleep can be as good (….and sometimes the parents come to the first visit with the tape already!).
The placement of a nasopharyngeal airway ('nasal trumpet') will provide immediate relieve of the obstruction and can be used acutely as a temporary measure in the child that is waiting for definitive treatment. It is usually well tolerated, but care must be taken of frequently suctioning secretions and evaluating patency.
Adenotonsillectomy should be taken as first step in management of children with OSAS, even in those with other airway abnormalities or problems. Children must be watched closely for the first 24 hours post surgery because of 2 potential problems: post-obstructive pulmonary edema (rare) and acute airway obstruction from surgical site edema (common). Most children will show dramatic improvement in the first 2 weeks following surgery, in a few improvements will be more slow in being noticed.
CPAP by nasal mask can be tried in those children who fail to adenotonsillectomy, and usually most children will accept it well, due to the relieve felt. This can also be used as bridge for those children awaiting for definitive surgical correction of craniofacial anomalies.
Tracheostomy should be reserved for children with cor pulmonale who fail
adenotonsillectomy and who have additional medical problems like neurologic
compromise, complicated craniofacial anomalies, or failure to more conservative
measures.
6. Alveolar Hypoventilation syndromes
Inadequate minute ventilation to sustain adequate gas exchange that becomes more pronounced (or manifests itself only) during sleep.
3 types: Congenital, acquired and transient.
A) Congenital syndromes: congenital hypoventilation syndrome (CHS), mild alveolar hypoventilation, late onset CHS, Arnold-Chiari type II malformation, Leigh disease, Pyruvate Dehydrogenase deficiency, Carnitine deficiency, Mobious syndrome.
B) Acquired: mostly the result of CNS injury from asphyxia, infection, trauma, tumor or infarction.
C) Transient: seen with severe, long-standing OSAS. Disappears once patient's hypoxic and hypercarbic ventilatory drives are reestablished.
CHS is the result of a deficient output from the brainstem respiratory centers. Generally does not affect the voluntary control of breathing, thus most affected individuals are able to maintain adequate ventilation while awake. Insensitivity of ventilatory and arousal mechanisms to hypercarbia and hypoxemia during sleep is a hallmark. Most will present in neonatal period, however in some children presentation is delayed until after infancy.
In most affected infants abnormalities during wakefulness will develop in later infancy, with an inadequate response to hypoxemia or hypercarbia and lack of perception of asphyxia. However, this is not progressive and after second or third year they may regain normal awake responses, particularly those who only had abnormal responses during sleep in the neonatal period.
Polysomnographic typical pattern is that of a normal respiratory rate but with pronounced hypopnea ( quiet shallow breathing). Findings are more dramatic during quite sleep than during REM sleep. Apneas are uncommon.
Respiratory stimulants (Xanthines, Doxapram, Progesterone, Methylphedinate) have been tried in children with CHS with variable success. Good results are usually obtained in children with the mildest forms of the disease, rarely in those with more severe manifestations.
Patients who fail to pharmacologic therapy are managed by mechanical ventilation, usually low setting, night-time ventilation through a tracheostomy. In older children different modalities of non-invasive ventilation can be tried. Diaphragmatic pacing has been used successfully for many years and without major complications. However, pacing can be used for up to 12 to 15 hours a day to avoid diaphragmatic fatigue and it has been used mostly for patients with adequate awake responses that require support only at night or for patients who require some support during the daytime but will like freedom from the ventilator for a number of hours during the day.
"Cyanotic Breath-Holding spells": apnea following a deep expiration and with rapid development of cyanosis.
Breath holding spells, with or wihtout cyanosis and of variable duration, are a common occurrence in early childhood. Approximately 3% of all children will have a "spell" at some point in time. This are benign and usually triggered by a sudden painful or unpleasant stimulus. Child looks like if attempting or starting to cry, but has a prolonged exhalation with no attempted inspiration for several seconds, during which change in color and posturing may ensue. Episode ends with a gasp followed by a deep inspiration, usually in response to external stimulation.
Cyanotic breath-holding spells of concern are those occurring in young infants, accompanied always by cyanosis, and resulting in loss of consciousness, seizures, and/or need for CPR to revert episode. Profound cyanosis, reflecting severe hypoxemia, develops rapidly and only few seconds after start of episode.
Mechanism underlying episodes is unclear. Sudden right-to-left intrapulmonary shunting has been demonstrated during episodes in affected children. Shunting possibly occurs at level of small pulmonary vessels (<20 diameter), and also seems to be consequence of sudden vasoconstriction of the pulmonary bed.
There is evidence for this sudden vasoconstriction to be centrally mediated,
mainly through excessive sympathetic activity in response to stress. Additionally,
these children have a lower threshold for vasoconstriction in response to
hypoxia.
Most children will respond to vigorous stimulation during an episode. The administration of oxygen by face mask also helps to quickly resolve the attack. Prognosis is generally considered to be good, mortality rate has been estimated around 1%. Most children 'outgrow' the problem by their 5th year. There is no evidence that children who suffered from cyanotic breath holding spells will subsequently have neurodevelopmental sequelae.
For severe cases with frequent episodes clonidine, an alpha-adrenergic central sympatholytic, has been used with variable success. Providing a calm enviroment, with avoidance of any emotional stressors, has also been found to be helpful.
Index Normal Physiology Development of Respiratory Control Definitions Specific Disorders Readings