Transcript urea cycle disorders

Case presentation
Dr.Mohammad Nemati
Congenital Diaphragmatic Hernia
 Case
:
A full-term male baby was born with
respiratory distress and cyanosis.
Physical examination showed barrel chest and
scaphoid abdomen. The breath sounds were
absent in the left side of the chest; the heart
sounds were best heard in the right side of the
chest.
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Labored respiration, nasal flaring, and sternal
retraction were found.
The baby weighed 2,800 g.
Blood pressure was 60/30 mm Hg; heart rate,
160 beats per minute; respiration, 70 breaths
per minute; and temperature, 36° C (96.8°
F).
ABG :
pH : 7.20
PaCO2 : 55 mm Hg
PaO2 : 35 mm Hg
HCO3 : 19 mEq per L.
Medical Disease and Differential
Diagnosis
Differential diagnoses:
Congenital cardiopulmonary anomalies
should be considered whenever cyanosis
and respiratory distress are present.
 A scaphoid abdomen is present due to
the absence of abdominal contents.
 The presence of the barrel chest, bowel
sounds in the chest, and the shift of heart
sounds to the right definitely suggest the
diagnosis of CDH.
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To confirm the diagnosis, a CXR should
be performed to demonstrate gas-filled
loops of bowel and probably the spleen
or liver in the chest.
 The lung on the side of the hernia is
compressed into the hilum, and the
mediastinum is shifted to the opposite
side of the chest.
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incidence and classification of CDH:
incidence : 1 in 2,500 to 3,000 births
male/female ratio is 2:1
the left diaphragm is more frequently involved
than the right (5:1)
practical
classification :
Absent diaphragm: Very rare
 Diaphragmatic hernia:
Posterolateral (Bochdalek): 80%
Anterior (Morgagni): 2%
Paraesophageal: 15% to 20%
 Eventration.: Very rare
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The causes of hypoxemia in patients with CDH:
Atelectasis resulting from compression of the
developed lung by the herniated abdominal
organs
 Pulmonary hypoplasia with a decrease in the
number of alveoli and bronchial generations.
 The hypoplastic lung will have abnormal
pulmonary vasculature resulting from a
disruption of normal development of the lung
tissue.
 PPH, causing increased right-to-left shunting
through a patent foramen ovale and ductus
arteriosus.
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The degree of pulmonary hypoplasia is
related to the timing of the herniation of
abdominal organs into the pleural cavity.
 The earlier herniation, the more severe
the pulmonary hypoplasia.
 Hypoplasia of the left ventricle may also
occur.
 The degree of pulmonary hypoplasia
determines the prognosis of CDH.
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The severity of pulmonary hypoplasia is
assessed by the intrapulmonary shunt or the
alveolar–arterial difference in oxygen tension
(PAO2–PaO2):
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(PAO2–PaO2) >500 mm Hg when breathing
100% oxygen is predictive of nonsurvival
(PAO2–PaO2) < 400 mm Hg is predictive of
survival
(PAO2–PaO2) between 400 and 500 mm Hg
represents a zone of uncertain prognosis.
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The severity of pulmonary hypoplasia may
also be evaluated by cardiac
catheterization and pulmonary angiogram
.
 Patients with severe pulmonary
hypoplasia typically will have a fixed rightto-left shunting at the level of the patent
ductus arteriosus or patent foramen
ovale caused by pulmonary hypertension.
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Persistent pulmonary hypertension (PPH) in CDH:
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several causes of PPH in these patients:
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Increased pulmonary vascular resistance and
pressure result from a hypoplastic lung.
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The pulmonary vasculature is abnormal, with a
decrease in volume and marked increase in
muscular mass in the arterioles.
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Right-to-left shunting of oxygen at the patent
foremen ovale and the PDA. This shunting
results in varying degrees of hypoxemia,
hypercarbia, and acidosis causing high
pulmonary vascular resistance and pressure.
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When pulmonary artery pressures are higher
than systemic pressures, right-to-left shunting
occurs across the ductus, resulting in higher PaO2
in the upper extremities than in the lower
extremities.
When right ventricular failure (precipitated by
pulmonary hypertension, progressive hypoxemia,
and acidosis or by closure of the ductus)
increases right atrial pressure to a level higher
than the left atrial pressure, right-to-left atrial
shunting ensues, producing further hypoxemia.
Left ventricular failure from hypoxemia and
acidosis induces systemic hypotension, resulting in
increased ductal shunting and hypoxemia. A
vicious cycle is established. Unless pulmonary
artery pressure is decreased, progressive hypoxia
and death may ensue.
Other congenital anomalies in newborns with CDH :
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Cardiovascular system: 13% to 23%
ASD,VSD, coarctation of aorta, and TOF
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CNS: 28%
spina bifida, hydrocephalus
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Gastrointestinal system: 20%
malrotation and atresia
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Genitourinary system:15%
hypospadias
Preoperative Evaluation and
Preparation
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How would you interpret this blood gases
and how would you correct them?
PH : 7.20
 Pco2 : 55 mmHg
 Po2 : 35 mmHg
 HCO3 : 19 mEq/liter
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The blood gases showed mixed respiratory and
metabolic acidosis and severe hypoxemia.
severe hypoxemia is caused by the pulmonary
pathologies and PPH.
Hypoxemia stimulates respiratory
chemoreceptors and causes
hyperventilation,resulting in respiratory
alkalosis initially.
However if hypoxemia is not corrected, the
patient will become exhausted and CO2
retention ensues.
Meanwhile, severe pulmonary hypoplasia may
cause CO2 retention, too .
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Severe hypoxemia induces anaerobic
metabolism, resulting in lactic acidosis. Systemic
hypotension, cause by kinking of major blood
vessels, particularly those of the liver, decreases
tissue perfusion, and futher contributes to lactic
acidosis.
Hypoxemia and respiratory acidosis should be
treated with mechanical ventilation and oxygen
therapy.
metabolic acidosis should be corrected by
administration of sodium bicarbonate and
improvement of circulation with fluid therapy.
What treatment should be given to improve
respiratory status preoperatively?
Immediate intervention should include
decompression of the stomach with an orogastric
or nasogastric tube and administration of
supplemental oxygen by mask.
 PPV by mask should be avoided to prevent
distention of the intrathoracic stomach, which will
further compress the lung and compromise
respiration.
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If cyanosis and hypoxemia persist , awake
intubation should be done to facilitate
mechanical ventilation .
Positive airway pressure during mechanical
ventilation should not exceed 25 to 30 cm H2O
to reduce the risk of tension pneumothorax.
Although pneumothorax can happen on either
side, it occurs more frequently on the
contralateral side of the hernia because the
pressure needed to expand the hypoplastic lung
is higher than that required to rupture the
normal lung.
Should CDH repaired urgently ?
In the past, CDH was a surgical emergency, in the
belief that the herniated contents caused lung
collapse and respiratory failure.
 It is now clear that lung compression by the
herniated viscera is a minor factor in the
cardiopulmonary compromise compared with the
pulmonary hypertension and hypoplasia.
 The consensus today is to delay surgery and
concentrate on medical stabilization. The goal of
preoprative therapy is to reverse the PPH that
results in right to left shunting across the PFO and
the PDA
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Improvement in the infant’s status is apparent
by improved oxygenation and ventilation.
doppler echocardiography may be used to
confirm the decreased pulmonary vascular
resistance.
The time it takes to stabilize the condition
varies from 24 to 48 hours in infants with only
mild pulmonary hypertension and hypoplasia
up until 7 to 10 days in neonates with severe
pulmonary hypertension and hypoplasia.
How would you treat PPH and improve oxygenation?
 continue
general anesthesia in the ICU , using
fentanyl 3 microgram/kg/h and pancuronium 0.1
mg/kg/h to blunt the autonomically mediated
cardiovascular response(pulmonary
vasoconstriction) to stimulation.
 minimize
endotracheal suctioning to avoid even
transient hypoxemia or decrease in FiO2.
 hyperventilate
the neonate with low tidal volume
and high respiratory rate 60 to 120/min to PH
7.55 to 7.60. respiratory alkalosis is the most
consistently effective therapeutic modality to
achieve pulmonary vasodilation.
 administer
pharmacologic vasodilators if the
above measures fail to control pulmonary
hypertension. Morphine,prednisolone
,chlorpromazine , phentolamine ,acetylecholine
,bradykinin , tolazoline,prostaglandin E1
,prostaglandin D2 and inhaled nitricoxide have
been tried with some success.
 moderately
restrict fluid to 2 to 4 ml/kg/h.
 ligate
the PDA to prevent shunting .this is
theoretically possible , but practically has been
associated with sudden right ventricular failure.
 support
with extracorporeal membrane
oxygenation(ECMO) if pharmacologic
intervention fails. ECMO has been associated
with a 50% to 65% survival rate.
The effects of NO on pulmonary and systemic
circulation?
Inhaled NO is a selective pulmonary vasodilator
and has no effect on systemic circulation because it
is inactivated immediately on exposure to
hemoglobin.some studies show improvement in
oxygenation in neonates with PPH exposed to 20
to 80 ppm NO.
 NO has been reported to be ineffective before
ECMO therapy in those CDH patients with
pulmonary hypoplasia.after ECMO followed by
surgery, NO was effective in improving
oxygenation.
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How is ECMO established?
Venovenous or venoarterial bypass is used.
 Venovenous bypass is established with a single
cannula through the internal jugular vein, with
blood removed from and infused into the right
atrium via separate ports.
 Venoartrial bypass is used preferentially by
some center because it provides the cardiac
support that is often needed. The right atrium is
cannulated via the internal jugular vein and the
aortic arch through the right common carotid
artery.
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What are the advantages of ECMO ?
 Diversion
of as much as 80% of cardiac output
from the right atrium into the extracorporeal
circuit immediately reduces or eliminates right
to left shunting through the foramen ovale or
ductus arteriosus.
 Right
ventricular work is decreased because of
reduced pulmonary blood flow and pressure.
 Pulmonary
vasoconstriction is reduced because
hypoxemia and acidosis are corrected by
ECMO. improved systemic oxygenation and
reduced ductal blood flow may lead to
spontaneous closure of the ductus arteriosus.
 The
hypoplastic lung is allowed to grow rapidly
and alveolar size is increased.
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incidence of bronchopulmonary dysplasia is
reduced since FiO2 and airway pressure are
lowerd by ECMO.
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The indications of ECMO :
Patients with severe hypoxemia and pulmonary
hypertension who do not responsd to maximal
conventional respiratory and pharmacologic
intervention .
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However, ECMO is associated with serious
complications of intracranial and pulmonary
hemorrahage.
The contraindications of ECMO :
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Gestational age < 35 weeks
Weight < 2000 gr
Preexisting intracranial hemorrhage
Congenital or neurologic abnormalities
incompatible with good outcome
> 1 week of aggressive respiratory therapy
Congenital heart disease
The optimal time to repair CDH :
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The baby is maintained on ECMO until the
pulmonary hypertension is reversed and
improvement in lung function is evident.
Doppler echocardiography may be used to
confirm the reverse of PPH. This is usually
seen within 7 to 10 days, but in some infants is
not apparent for up 3 weeks.
Newborns who do not demonstrate
significant improvement over this time have
pulmonary hypoplasia that will not benefit
from further extracorporeal life support.
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Timing of repair of the CDH on ECMO is
contraversial.
Some centers prefer early repair to allow a
greater duration of postrepair ECMO,
whereas many centers defer repair until the
infants has demonstrate the ability to tolerate
weaning from ECMO support.
What other measures should you take to
prepare the patient for surgery?
The patients should be examined carefully for
the presence and severity of associated
congenital anomalies. Those patients with
congenital heart disease have significantly
increased mortality.
 Hypothermia should be prevented and
corrected, since hypothermia can increase
oxygen consumption and result in further
hypoxemia and acidosis. The neonate should be
maintained in a neutral thermal enviroment of 30
to 40 ° C .
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Laboratory studies should include ABG ,CBC,
electrolytes, blood sugar, blood type,and
crossmatch for blood products.
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Venous access should be ready prior to
surgery. Peripheral veins in the upper
extremities are preferred because reduction of
the hernia often increases abdominal pressure
and partially obstructs the inferior vena cava,
making lower extremity veins less reliable.
Neck vein are avoided in case ECMO is
required.
How would you premedicate this patient?
No premedication should be given to the
neonate with CDH.
 The newborn dose not have any anxiety
,and sedatives may just further depress
the already compromised
cardiopulmonary function.
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Intraoperative Management
What monitors would you use for this neonate
during surgery?
Respiratory:
 Precordial and esophageal stethoscope
 Pulse oximeter, both above and below nipple for
preductal and postductal oxygen saturation.
 Capnometer
 Inspiratory pressure gauge
 Inspiratory oxygen concentration
 ABG
Cardiovascular:
 ECG
 Doppler blood pressure device
 Precordial stethoscope
 Arterial line- right radial artery for preductal
PaO2
 Central venous pressure line for evaluating
volume status and right ventricular performance
Thermoregulatory
 Esoghageal or rectal temperature probe
How would you induce and maintain anesthesia?
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If the neonate has not been intubated, awake
intubation should be done after
preoxygenation.
However, if the neonate is too vigorous for
awake intubation, he can be intubated without
a muscle relaxant after breathing halothane
and oxygen spontaneosly.
Positive pressure ventilation should be avoided
before intubation to prevent gastric distention
and further compromise of respiration.
The choice of anesthetics depends on the severity
of cardiovascular dysfunction.
 Patients in shock and severe hypoxemia may
tolerate only oxygen and a nondepolarizing
relaxant such as pancuronium or vecuronium.
 if blood pressure is adequate and stable, halothane
or fentanyl in addition to a muscle relaxant, often
pancuronium, may be titrated to maintain
anesthesia.
 fentanyl and pancuronium may be continued
postoperatively to control ventilation and
minimize hormonal response to stress, which may
increase pulmonary hypertension.
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NO should not be used in patient with CDH
before hernia reduction and abdominal closure.
 Because NO has higher diffusion capacity than
nitrogen(35:1), the amount of NO diffused from
blood to the gut is much more than the amount of
NO diffused frome the gut to the blood.
 Therefore, NO may distend the intrathoracic gut
and compress the functioning lung tissue, further
compromising pulmonary function.moreover, a
distended gut may cause difficulty in abdominal
closure and may increase abdominal pressure,
compressing the inferior vena cava and resulting in
hypotension.
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Would you use 100% oxygen during anesthesia?
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Selection of the appropriate inspired
concentration of oxygen depends on the
severity of pulmonary dysfunction.
Retrolental fibroplasis is a potential danger
during neonatal anesthesia.
Current guideline suggest that infants are at
risk for retrolental fibroplasia until 44 to 50
weeks of gestational age.
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However, hypoxia cause pulmonary
vasoconstriction and pulmonary hypertension
wich may increase right-to-left shunting of
desaturated blood at preductal or ductal level.
therefore, air or nitrogen is added to oxygen if
the PaO2 on 100% oxygen is> 90 to 100 mm
Hg.
PaO2 should be optimally kept at 80 to 100
mm Hg or the arterial oxygen saturation
between 95% to 98%.
How would you ventilate the patient?
Ventilation is controlled either manually or by a
respirator. Small tidal volumes should be used
to keep the airway pressure below 20 to 30 cm
H2O in order to prevent contralateral
pneumothorax .
 High respiratory rates (60 to 120 breaths/min)
should be adjusted to achieve hyperventilation
to PaCO2 between 25 to 30 mm Hg in order
to lower pulmonary vascular resistance and
minimize right-to-left shunting through the
ductus arteriosus.
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The following steps are used to maintain body
temperature:
 warm
the operating room to 80° F( 27° C).
 use radiant warming lamps and a heating
blanket.
 warm and humidify inspired gases.
 warm transfused blood and intravenous fluid to
37 ° C.
The surgeon returned the intrathoracic stomach
and intestine to the peritoneal cavity and the
ipsilateral lung was found to be hypoplastic and
collapsed.
The resident anesthesiologist tried to expand the
collapsed lung manually with positive airway
pressure.
Five minutes after the abdomen was closed, the
blood pressure suddenly dropped from 70/40 to
30/20 mm Hg, the heart rate from 150 to 80/min
And the pulse oximeter from 95% down to 60%
saturation. What would you do immediately?
Any sudden deterioration in blood pressure,
heart rate, oxygen saturation, or pulmonary
compliance is suggestive of tension
pneumothorax.
 Auscultation of the chest, especially the
contralateral side, should be done immediately.
If absent or diminished breath sounds confirm
the diagnosis, a chest tube should be inserted
right away.
 A large-bore intravenous catheter with needle
may be inserted to release the tension
pneumothorax if a chest tube is not
immediately available.
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The tension pneumothorax is usually on the
contralateral side since the high airway pressure
required to inflate the hypoplastic lung may
rupture the normal alveoli on the contralateral
side, resulting in pneumothorax. Moreover, the
ipsilateral chest usually already has a chest tube
after surgery.
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If there is no pneumothorax or deterioration is
not improved after insertion of a chest tube,
inferior vena cava compression (causing
decreased venous return and decreased cardiac
output) should be considered.
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The peritoneal cavity is often underdeveloped
and unable to fully accommodate the returned
abdominal organs, wich increases the
intraabdominal pressure.
In this circumstance, the abdominal wound
should be opened to relieve the compression
on the vena cava and diaphragm. A silastic
patch may be used to cover the abdominal
defect temporarily, and the defect will be
closed at a later time.
Fluid therapy in this patient :
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Fluid therapy should be aimed to correct the
preoperative deficit, provide maintenance fluid,
and replace intraoperative,third space, and
blood losses.
Kidneys are 80% to 90% mature by 1 month
of age. Before that time, the infant cannot
tolerate the extremes of renal stress.
Neonate are sodium losers, therefore,
exogenous sodium should be supplied.
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Neonates have decreased glycogen storage
and are prone to hypoglycemia after brief
periods of starvation. Therefore, glucose
should also be provided.
However, hyperglycemia may predispose the
patient to intracranial hemorrhage and should
be avoided.
Preoperative fluid deficit may be evaluated by
careful history taking, signs and symptoms of
dehydration , urine output, and central venous
pressure(CVP) monitoring.
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Maintenance fluids consisting of 5% dextrose in ¼
to ½ saline are given at 4 ml/kg/h.
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Intraoperative evaporative and third space losses
are replaced with Ringer’s lactate or saline at
approximately 8 to 10 ml/kg/h.
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Each milliliter of blood loss is replaced with 3 ml
of Ringer’s lactate or 1 ml of 5% albumin in saline.
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Blood pressure, heart rate, urine output ,CVP,
hematocrit, and sodium and glucose levels are
monitored to follow the fluid therapy.
At the conclusion of surgery, would you extubate
the patient in the operating room?
The patient should not be extubated in the
operating room .
 Because varying degrees of pulmonary
dysfunction are always present postoperatively.
 The endotracheal tube should be left in place
and the baby should be transported to the ICU
for further postoperative care.
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Postoperative management
Postoperative problems in this patient:
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The postoperative course is often characterized
by a “honeymoon” period of rapid improvement,
followed by sudden deterioration with profound
arterial hypoxemia, hypercapnia, and acidosis.
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The mortality in patients with CDH varies from
30% to 60% .
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The factors affecting the mortality include
the following:
 Pulmonary
hypoplasia
 Associated congenital defects-cardiovascular and
central nervous systems
 Inadequate preoperative management,
hemorrhage, tension pneumothorax, inferior
vena cava compression, persistent fetal
circulation, and excessive suction on chest tube.