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Special considerations in the premature and ex-premature infant
After reading this article, you should be able to:
define the terms prematurity, extreme prematurity and
list the well-known complications of premature infants
explain the basic principles of anaesthetizing a
RDS may be complicated by air leak (pneumothorax, pneu-
Mean survival rates for babies born at 24 weeks and 27 weeks are
momediastinum, pulmonary interstitial emphysema) and lead to
currently 50% and 90% respectively, although levels of morbidity for
bronchopulmonary dysplasia (BPD) and chronic lung disease
the most premature infants may be high. This article describes the clinical
conditions unique to the premature and ex-premature infant, and some
BPD is defined as oxygen dependency for more than 28 days
common surgical procedures and special considerations for the conduct
after birth and an abnormal chest radiograph. The chest radio-
of anaesthesia in this vulnerable population.
graph changes in early BPD may be indistinguishable from theground glass appearance of RDS, but later radiographs show
Keywords Apnoea; pain; premature infant; respiratory distress
patchy atelectasis and cystic changes with hyperexpansion and
The course of RDS has been greatly ameliorated by modern
neonatal intensive care practice. Exogenous surfactant isadministered prophylactically within hours of birth. Nasal
continuous positive airway pressure (nCPAP) is the method of
choice for ventilatory support, and results in an increase in
Full-term neonate: 37e42 weeks’ gestation and aged less than
functional residual capacity (FRC), reduction in atelectasis and
improved work of breathing. Intermittent positive pressure
Premature neonate: less than 37 weeks’ gestation.
ventilation (IPPV) increases the risk of BPD and is used only if
Extreme preterm neonate: less than 28 weeks’ gestation.
necessary (e.g. for the administration of surfactant, for VLBW
Post-conceptional age: gestational age plus post-natal age.
infants at <28 weeks, and if oxygenation with nCPAP is inade-
Low birth weight (LBW): less than 2500 g.
quate with a fraction of inspired oxygen (FiO
Very low birth weight (VLBW): less than 1500 g.
Babies are extubated to nCPAP as soon as possible.
Extremely low birth weight (ELBW): less than 1000 g.
Different ventilation modes are used to reduce volu/baro-
trauma. These include various forms of patient-triggered venti-
lation (such as pressure support and proportional assist
The neonatal period is one of major physiological changes, with
ventilation) and minimization of excessive tidal volumes
transition from intrauterine to extrauterine life. The premature
(volume targeted ventilation and high frequency
infant has to undergo these same changes, but in the context of
The use of strategies to allow permissive hypercapnia may also
reduce the risk of ventilator-induced injury.
Steroids have an adverse effect on development of the brain
Respiratory distress syndrome and chronic lung disease
and are no longer used to facilitate weaning from long-term
Respiratory distress syndrome (RDS) results from immaturity of
the lungs, particularly the production of surfactant in the
CLD occurs in 15e50% of VLBW infants. The severity of CLD
premature infant. RDS is typified by tachypnoea, dyspnoea,
is estimated from the duration of nCPAP and oxygen depen-
cyanosis and ‘grunting’, non-compliant lungs, widespread atel-
dency, rather than the duration of ventilation.
ectasis on chest radiograph and the presence of hyaline
Ex-premature babies are susceptible to respiratory infection in
membranes in terminal airways (previous terminology: hyaline
childhood, particularly in the first year of life. Reversible
obstructive airway disease is common and they may have
RDS is invariable in infants born at less than 28 weeks’
acquired subglottic stenosis as a consequence of prolonged
Antenatal corticosteroid administered to mothers in preterm
labour induces surfactant production and reduces the incidence
Apnoea is a pause in breathing of more than 20 seconds or one ofless than 20 seconds associated with bradycardia and/orcyanosis.
Guy Bayley MB BS MRCP MRCPCH FRCA is a Consultant Paediatric
Apnoea of prematurity is commonly seen in neonatal units,
Anaesthetist at Bristol Royal Hospital for Children, Bristol, UK. Conflicts
and may be classified as central (brainstem, peripheral chemo-
receptor immaturity), obstructive (reduced tone, asynchrony of
Ó 2010 Elsevier Ltd. All rights reserved.
diaphragm/upper airway activity, excessive neck flexion, struc-
signs progressing to apnoea with shock and disseminated intra-
tural abnormalities) or of mixed cause.
vascular coagulation (DIC). Intestinal perforation may cause
In adult life, hypoxia and hypercapnia increase ventilation.
a localized mass and the abdominal wall may be reddened in the
Premature and newborn term babies respond to hypoxia by
presence of peritonitis. NEC is associated with pneumatosis (gas
a brief increase in ventilation followed by apnoea and have
within the bowel wall), and a characteristic appearance on
a blunted response to hypercapnia. In the term infant, normal
a radiograph of dilated thickened loops of bowel with intramural
responses to hypercapnia and hypoxia are seen by 3 weeks of
gas. Free gas may be visible on horizontal shoot-through in the
age, but this is delayed in premature infants.
presence of a perforation. Investigations may also reveal low
Apnoea in premature infants is exacerbated by hypoxia,
platelet count, raised C-reactive protein and metabolic acidosis.
sepsis, intracranial haemorrhage, metabolic abnormalities,
Babies with severe disease may have exposed T antigen on red
hypo/hyperthermia, upper airway obstruction, heart failure,
blood cells, which leads to haemolysis in the presence of trans-
anaemia, vasovagal reflexes and drugs, including prostaglandins
fused blood products containing anti-T antibodies. Blood prod-
ucts with low-titre anti-T antibodies will be required for
Apnoeas are treated by stimulation, bag-mask ventilation,
T-antigen-positive infants (packed cells reconstituted in SAG-M
addressing underlying abnormalities, the use of respiratory
stimulants such as caffeine or aminophylline, nCPAP or
Treatment of NEC consists of general supportive measures,
antibiotics, and resting the gut with 7e10 days of total parenteral
Term neonates are at low risk of postoperative apnoea after
nutrition. Half the infants with NEC require surgery for intestinal
routine minor surgery at 44 weeks post-conception. However, in
perforation or following failure of medical treatment. Surgical
premature neonates the probability of postoperative apnoeas
options include: laparotomy for resection of necrotic bowel and
decreases to less than 1% only at 60 weeks post-conception.
formation of a proximal stoma and distal mucous fistula; gutresection and primary anastomoses; placement of a peritoneal
drain in those unsuitable for laparotomy; or for infants with
The arterial duct is one of the fetal shunts and is closed in 3e4
inoperable disease, proximal defunctioning jejunostomy and
days in 90% of term and ‘well’ premature babies. The duct closes
‘second look’ laparotomy at 24 hours if the baby survives.
in response to a rise in oxygen tension after birth and a fall incirculating prostaglandins. Patent ductus arteriosus (PDA) is
seen in 50% of VLBW infants due to low oxygen tension,
Survival of extreme preterm infants has improved considerably
continuing high prostaglandin levels, or abnormal stimuli such
in recent years. However, 21% of babies born at less than 25
as acidosis and expansion of the circulating volume.
weeks’ gestation have severe disability, and 41% have significant
Aorto-pulmonary shunting though the PDA causes high
cognitive impairment. A major determinant of cerebral impair-
pulmonary blood flow, worsening RDS, cardiac failure and low
ment is germinal matrix intraventricular haemorrhage (IVH),
diastolic pressure. PDA is a risk factor for intraventricular hae-
particularly complicated by ventricular enlargement, paren-
morrhage, necrotizing enterocolitis and CLD. PDA typically
chymal infarction or cystic periventricular white-matter injury.
becomes symptomatic at 5e10 days as pulmonary vascular
Major IVH usually occurs within the first few days of life and is
resistance falls; it presents with worsening respiratory function,
bounding pulses, a continuous murmur and chest radiograph
Factors that have been shown to increase the incidence of IVH
that shows cardiomegaly and increased lung shadowing. Diag-
or later neurodevelopmental delay include RDS, hypotension or
nosis is confirmed by echocardiography.
fluctuating blood pressure, the use of hypertonic infusions and
Conventional treatment for symptomatic PDA is fluid restric-
tion, diuretics (furosemide) or medical closure with indometh-
The normal lower limit of mean arterial blood pressure (MAP)
is roughly equivalent to the gestational age on the first day of life,
(NSAIDs) may worsen renal function, and have been associated
with a MAP of at least 30 mmHg for all infants by day 3 of life.
with gastrointestinal haemorrhage and perforation. These agents
Management of hypotension requires judicious use of volume
are contraindicated in the presence of thrombocytopenia.
expansion (crystalloid or colloid) and the early use of inotropic
Surgical closure of symptomatic PDA is indicated for failed
agents such as adrenaline, dopamine or dobutamine. Aggressive
medical treatment or when NSAIDs are contraindicated.
volume expansion should be avoided, especially in the first fewdays of life.
Periventricular leukomalacia describes histological changes in
Necrotizing enterocolitis (NEC) occurs mainly in preterm infants,
periventricular white matter seen in premature infants. The
with an incidence of about 7% and a mortality of 15e30%. It has
pathogenesis of periventricular leukomalacia is associated with
a multifactorial aetiology, but common features include prema-
hypoxic-ischaemic or toxic injury, infection, impaired cerebral
turity and poor mucosal integrity, hypoxia, early feeding with
autoregulation, cerebral ‘steal’ due to a large PDA and severe
formula milk and colonization with pathogenic bacteria.
hypocarbia. Bilateral occipital cystic periventricular leukomalacia
NEC causes inflammation and transmural necrosis and can
is a very strong predictor of cerebral palsy.
affect any part of the intestine, typically the terminal ileum,caecum and ascending colon. The classical presentation is of
Retinopathy of prematurity and oxygen toxicity
abdominal distension, bloody stool and bile-stained aspirates,
Retinopathy of prematurity (ROP) is seen in LBW infants less
but signs of sepsis may predominate, with vague non-specific
than 32 weeks’ gestation. Hyperoxia in the first weeks of life
Ó 2010 Elsevier Ltd. All rights reserved.
causes vasoconstriction of retinal vessels, which leads to retinal
the infant. Disadvantages include limited access and light for
ischaemia and a subsequent vasoproliferative phase. Good
surgeons. Laparotomy for NEC may be difficult because of
neonatal care, ophthalmic screening and treatment can prevent
hypovolaemia, significant third-space losses, bleeding and coa-
gulopathy. Extreme care should be taken if transporting the
There is concern that even brief exposure to high oxygen
neonate to theatre, in particular not to displace intravenous lines
levels is associated with increased morbidity and mortality in
VLBW infants; fluctuations in oxygen levels should be avoided
Anaesthesia monitoring should be as standard for any oper-
and oxygen saturation maintained between 88e95%, not
ating room. Ventilator dead-space should be minimized but end
exceeding 95%. Newborn resuscitation should be carried out
tidal carbon dioxide may still significantly under-read. A T-piece
with room air rather than 100% oxygen.
should be available for hand ventilation with an air/oxygenmixer. Oxygen saturation should not exceed 95%.
Invasive arterial monitoring is useful in the septic patient
Thermoregulation in the neonate is limited and easily over-
receiving inotropes, or when cardiovascular stability is antici-
whelmed by environmental conditions. There is a great potential
pated. An umbilical arterial catheter may be present from birth;
for heat loss (high body surface area to body weight ratio,
its distal end should be sited above the diaphragm between the
increased thermal conductance, increased evaporative heat loss
sixth and tenth vertebrae. Peripheral arterial cannulation (radial,
through the skin) and limited heat production through brown fat
posterior tibial, dorsalis pedis) is aided by a ‘cold’ light. The
metabolism. The preterm baby is particularly vulnerable as the
femoral or axillary artery may be used. The brachial artery
immature skin is thin and allows major heat (and evaporative
should be avoided because it is an end artery with poor collateral
fluid) losses. The principle of anaesthesia in these infants is for
minimal handling in a warm environment.
Central venous access may be useful if large-volume trans-
fusions are anticipated or inotropes are required. An umbilical
venous catheter may be present from birth and is useful for the
Pain pathways develop during the second and third trimester. By
first week of life. The tip of the umbilical venous catheter should
26 weeks’ gestation premature neonates respond to tissue
be in the inferior vena cava at the level of (but not in) the right
damage by withdrawal reflexes and activation of the stress
atrium. Ultrasound guidance may be useful to aid in femoral
response. Pathways between the thalamus and somatosensory
cortex function by 29 weeks’ gestation. The precise gestational
Blood for transfusion and a means for warming infused fluids
age when a neonate is able to perceive pain is unknown.
The temperature of the operating room should be raised to
Anaesthetic agents in the premature infant
25 C and there should be a means of warming the baby (overhead
Recent work has investigated the effects of exposure of the
developing brain to anaesthetic drugs such as midazolam,
The surgical drapes should be lightweight, ideally transparent
nitrous oxide, isoflurane and ketamine. In animal experiments
plastic, so that the baby (and the tracheal tube) can be clearly
prolonged exposure to these agents were found to cause wide-
seen. Drapes should not be stuck to the fragile skin. The surgeons
spread apoptosis with persistent memory/learning impairments.
must not rest their hands on the infant.
The mechanism appears to be due to blockade of glutamate and
Anaesthesia should be induced only when all are fully
g-aminobutyric acid receptors. The relevance to clinical practice
prepared. The baby is intubated orally, either with an uncuffed
is unclear, but only essential surgery should be performed in
tracheal tube (2.0e3.0 mm internal diameter (ID)). The tracheal
tube should be carefully strapped in place (not tied to a bonnet),and the position rechecked every time the infant is moved.
Conduct of anaesthesia in the premature infant
Avoid hyperventilation, oxygen saturation greater than 95%,
General considerations: anaesthesia and surgery in the prema-
high-peak inspiratory pressures and barotrauma. Permissive
ture neonate is high risk, require careful collaboration with the
neonatal intensive care unit (NICU), and close attention to detail
Isotonic fluids should be used during surgery (0.9% saline,
Hartmann’s or Ringer’s lactate), given as boluses of 10e20 ml/kg
Consent should be discussed with the parents and questions
and titrated to blood pressure, heart rate, capillary refill time and
base excess if available. Avoid swings in blood pressure and
A full history should be taken, with particular note of
excessive volume loading. Blood should be transfused to main-
cardiorespiratory status, acidebase balance, full blood count
tain a haematocrit of 36% in the newborn infant (high levels of
(including platelet count), coagulation, urea, and electrolytes,
fetal haemoglobin) and 30% in the chronically transfused infant.
Blood glucose should be monitored and glucose-containing
The baby should be carefully examined. Identify the site and
maintenance fluids continued during surgery (e.g. 10% dextrose
state of intravenous lines. If intubated, assess bilateral air entry,
size and length of the tracheal tube, recent chest radiograph and
Multimodal analgesia should be used for pain relief (e.g.
regional anaesthesia, local anaesthetic infiltration, paracetamol
Surgery can take place in the NICU (PDA ligation is frequently
and opioids, most commonly fentanyl). Epidural catheters can be
performed in the NICU). The advantages are a thermoneutral
inserted via the caudal route. Sucrose analgesia may be useful in
environment, use of neonatal ventilator and minimal handling of
the NICU for painful interventions such as cannulation.
Ó 2010 Elsevier Ltd. All rights reserved.
The child may have CLD, reduced lung compliance, reversible
Regional anaesthesia (spinal or caudal anaesthesia) may be
obstructive airway disease, gastro-oesophageal reflux, impaired
suitable in experienced hands and may reduce postoperative
renal concentrating ability, chronic anaemia, failure to thrive,
apnoeas, provided supplemental sedation is avoided.
neurodevelopmental delay and/or seizures, subglottic stenosis
Anaesthesia for ventriculoperitoneal shunt
Prolonged exposure in a cold theatre may result in
The child will be susceptible to postoperative apnoeas up to
60 weeks post-conception and may require postoperative nCPAP
May require morphine for postoperative analgesia
or ventilation; oral caffeine may be considered, particularly if
(in combination with paracetamol and ibuprofen); the child is at
Careful preoperative resuscitation and correction of acidebase
balance and coagulopathy. Platelet transfusion and fresh-frozen
1 Greenough A, Premkumar M, Patel D. Ventilatory strategies for the
extremely premature infant. Pediatr Anaesth 2008; 18: 371e7.
Fluid shifts during surgery may be significant, requiring up to
2 Tan A, Schulze A, O’Donnell CPF, Davis PG. Air versus oxygen for
60e80 ml/kg of volume resuscitation.
resuscitation of infants at birth. Cochrane Database Syst Rev 2004; 3.
Careful positioning for left thoracotomy and placement of clip
Bingham R, Lloyd Thomas A, Sury M, eds. Hatch and Sumner’s textbook of
Place pulse oximeter or arterial line on lower half of the body to
paediatric anaesthesia. Edinburgh: Churchill Livingstone, 2007.
detect accidental ligation of descending aorta; persistent desatu-
Cote C, Lerman J, Todres D. A practice of anesthesia for infants and
ration after reinflation of the lung indicates accidental ligation of
children. 4th edn. Saunders Elsevier, 2010.
pulmonary artery. Correct placement of clip is indicated by rise in
Dalens B. Anesthesia at early ages. Best Pract Res Clin Anaesthesiol
blood pressure, particularly diastolic blood pressure.
Intercostal nerve block by surgeon is useful (under direct
Management of the neonate: anaesthetic considerations. In:
Bissonnette B, Dalens B, eds. Principles and practice of pediatric
anaesthesia. Philadelphia: McGraw-Hill, 2003.
Caudal anaesthesia or ilioinguinal nerve block and para-
Rennie J, ed. Roberton’s textbook of neonatology. 4th edn. Oxford:
cetamol for postoperative analgesia can be used.
Ó 2010 Elsevier Ltd. All rights reserved.
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Comisión de Evaluación de Medicamentos SITAGLIPTINA 1.- IDENTIFICACIÓN DEL FÁRMACO Y AUTORES DEL INFORME Fármaco: Sitagliptina Indicación clínica: En pacientes con diabetes mellitus tipo 2 para mejorar el control glucémico, en combinación con metformina, una sulfonilurea, una sulfonilurea + metformina, o un agonista del receptor activado por el proliferador de per