Saturday, June 3, 2017

Spinal Injury - Initial Assessment



SCI must  be presumed until excluded.
Studies recorded missed injury rate as high as 33%. Delayed or missed diagnosis is usually attributed to failure to suspect an injury to the cervical spine, or to inadequate cervical spine radiology and incorrect interpretation of radiographs. An appropriate procedure for the evaluation of the potentially unstable spine must be robust and easy to implement, with a high sensitivity, given the potential importance of such injuries. It must also address the main issues raised by the modalities available for diagnosis.
For spinal trauma, the main concerns are which patients can be cleared by clinical exam alone, how many plain X-rays are necessary and when should additional imaging using Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) be used. An assessment for ligamentous injury in the absence of a fracture is also important, especially in unconscious patients who are unable to complain of neck pain or tenderness.
While it is tempting to focus on the cervical spine, it is important to assess and clear the entire spinal column. The thoracolumbar spine, while more protected, is at risk in major trauma and must be assessed both clinically and radiologically. Additionally, 5% of spinal injuries have a second, possibly non-adjacent, fracture elsewhere in the spine.
These pages discuss the initial assessment and management of the potentially spine injured patient. The actual protocol implemented at any given institution will depend on the expertise and facilities available. Where the required expertise or imaging are not available in a given institution, the protocol should encompass criteria for expeditious transfer of patients to specialist care.

Spinal Stabilization & Management



Spinal immobilization is a priority in multiple trauma,
spinal clearance is not.



Indications for spinal immobilization

Very few studies define the criteria used to decide who is at risk from cervical spine injury.
Blunt Injury All patients with sufficient mechanism of injury to lead to a spinal injury should be considered to have a spinal injury until proven otherwise. What constitutes 'sufficient mechanism' is undefined.
Penetrating Injury Gunshot wounds that have traversed the spinal column may produce unstable injuries and caution should be exercised. Gunshot wounds to the cranium alone are not associated with a risk of cervical spine trauma. It is not necessary to immobilize stab injuries. Spinal immobilization devices may interfere with the recognition and management of life-threatening conditions.

Techniques of immobilization and patient handling

The spine should be protected at all times during the management of the multiply injured patient. The ideal position is with the whole spine immobilised in a neutral position on a firm surface. This may be achieved manually or with a combination of semi-rigid cervical collar, side head supports and strapping. Strapping should be applied to the shoulders and pelvis as well as the head to prevent the neck becoming the centre of rotation of the body.

Prehospital

Manual spinal protection should be instituted immediately. The application of definitive immobilisation devices should not take precedence over life-saving procedures.
If the neck is not in the neutral position, an attempt should be made to achieve alignment. If the patient is awake and co-operative, they should actively move their neck into line. If unconscious or unable to co-operate this is done passively. If there is any pain, neurological deterioration or resistance to movement the procedure should be abandoned and the neck splinted in the current position.
Long spine (rescue) boards are valuable primarily for extrication from vehicles. Repeated transfers to and from the board may compromise spinal protection and induce a significant amount of spinal movement. Patients may also be transferred on a scoop stretcher and/or vacuum mattress. There is little place for the short spine board or spinal extrication devices in the prehospital environment.

In-hospital

The spine board should be removed as soon as possible once the patient is on a firm trolley. Prolonged use of spine boards can rapidly lead to pressure injuries. Full immobilisation should be maintained. Manual protection should be reinstated if restraints have to be removed for examination or procedures (eg. intubation).
The log-roll is the standard manoeuvre to allow examination of the back and transfer on and off back boards. Four people are required, one holding the head and coordinating the roll, and three to roll the chest, pelvis and limbs. The number and degree of rolls should be kept to an absolute minimum. Rigid transfer slides (eg. Patslide) are useful for transferring the patient from one surface to another (eg CT scanner, operating table).
Patients who are agitated or restless due to shock, hypoxia, head injury or intoxication may be impossible to immobilise adequately. Forced restraints or manual fixation of the head may risk further injury to the spine. It may be necessary to remove immobilisation devices and allow the patient to move unhindered.
Anaesthesia may be necessary to allow adequate diagnosis and therapy. Intubation of the trauma victim is best achieved via rapid sequence induction of anaesthesia and orotracheal intubation, though the technique used should ultimately depend on the skills of the operator. The collar should be removed and manual, in-line protection re-instituted for the manoeuvre. The routine use of a gum elastic bougie is recommended, minimising cervical movement by allowing intubation with minimal visualisation of the larynx.

Transfer to Secondary Units

Patients may require transfer to other units for definitive care of other injuries such as head or pelvic trauma. There should be no unnecessary delays in the transport of these patients. Transfer should not wait for unnecessary diagnostic procedures that will not alter management. This includes radiological imaging of the spine.
The spine should be immobilised and protected for the transfer. Split-scoop stretchers and vacuum mattresses are more appropriate for transfer than rigid spinal (rescue) boards, which should be reserved for primary extrication from vehicles, rather than as devices for transporting patients.

Spinal Clearance

  1. Spinal immobilisation is a priority in multiple trauma, spinal clearance is not.
  2. The spine should be assessed and cleared when appropriate, given the injury characteristics and physiological state.
  3. Imaging the spine does not take precedence over life-saving diagnostic and therapeutic procedures.

Clinical clearance of Cervical Spine Injury

Numerous large prospective studies have described the large cost and low yield of the indiscriminate use of cervical spine radiology in trauma patients. Although there are case reports of bony or ligamentous injuries in asymptomatic patients, no asymptomatic patient in the literature has had an unstable cervical spine fracture or suffered neurological deterioration due to the injury. There is no conclusive evidence in the literature that supports clinical clearance of the spine in the prehospital environment. There is enough variation between prehospital and in-hospital assessments to recommend that prehospital removal of spinal immobilisation be avoided. Mechanism of injury alone does not determine the need for radiological investigation.
The cervical spine may be cleared clinically if the following preconditions are met:
  • Fully alert and orientated
  • No head injury
  • No drugs or alcohol
  • No neck pain
  • No abnormal neurology
  • No significant other 'distracting' injury (another injury which may 'distract' the patient from complaining about a possible spinal injury).
Provided these preconditions are met, the neck may then be examined. If there is no bruising or deformity, no tenderness and a pain free range of active movements, the cervical spine can be cleared. Radiographic studies of the cervical spine are not indicated.

Conscious, Symptomatic Patients

  1. Radiological evaluation of the cervical spine is indicated for all patients who do not meet the criteria for clinical clearance as described above.
  2. Imaging studies should be technically adequate and interpreted by experienced clinicians.

Plain Film Radiology

The standard 3 view plain film series is the lateral, antero-posterior and open-mouth view.
The lateral cervical spine film must include the base of the occiput and the top of the first thoracic vertebra. The lateral view alone is inadequate and will miss up to 15% of cervical spine injuries. The lower cervical spine may be difficult to examine and caudal traction on the arms should be used to improve visualisation. Repeated attempts at plain radiography are usually unsuccessful and waste time. If the lower cervical spine is not visualised a CT scan of the region is indicated. How to read the lateral cervical spine film.
The antero-posterior view must include the spinous processes of all the cervical vertebrae from C2 to T1.
The open-mouth view should visualise the lateral masses of C1 and the entire odontoid peg. Bite blocks may improve the open-mouth view. In the unconscious, intubated patient the open mouth view is inadequate and should be replaced by a CT scan from the occiput to C2.
The addition of two oblique views to the standard 3-view series does not increase the sensitivity of plain film evaluation. Some centres use two supine or trauma-oblique views to replace the antero-posterior view. These views can provide excellent visualisation of the posterior elements of the cervical spine and provide significantly more information than the antero-posterior view. Lateral

CT Scanning

Thin-cut (2mm) axial CT scanning on specific bone windows, with sagittal and coronal reconstruction should be used to evaluate abnormal, suspicious or poorly visualised areas on plain radiology. With technically adequate studies and experienced interpretation, the combination of plain radiology and directed CT scanning provides a false negative rate of less than 0.1%. The scan should include the entire vertebral body above and below the region of interest, as these must be undamaged for subsequent internal fixation.

Assessment of soft tissue injury in the awake patient

The patient with normal radiological evaluation as described above who has persistent symptoms requires an evaluation of soft tissue injury with static flexion and extension imaging of the neck at the extremes of the active range of motion. Pure disc or ligamentous disruption can produced unstable cervical spine injuries and will usually be detected by such imaging. The movements are safe provided the patient performs them actively and halts if there is an increase in pain or neurological symptoms.

Magnetic Resonance Imaging

All patients with an abnormal neurological examination should be evaluated in a specialist unit and have an MRI scan of the spine. Patients who report transient neurological symptoms (the 'stinger' or 'burner') but who have a normal exam should also undergo an MRI assessment of their spinal cord.

Unconscious, Intubated Patients

  1. The odontoid view is unreliable in intubated patients.
  2. Clinical examination is impossible in the unconscious patient.
  3. Plain film radiology cannot exclude ligamentous instability.
The standard radiological examination of the cervical spine in the unconscious, intubated patient is :
  • Lateral cervical spine film
  • Antero-posterior cervical spine film
  • CT scan of occiput - C3
The open-mouth odontoid radiograph is inadequate in intubated patients and will miss up to 17% of injuries to the upper cervical spine.
Thin-cut (2mm) axial CT scanning on specific bone windows, with sagittal and coronal reconstruction should be used to evaluate abnormal, suspicious or poorly visualised areas on plain radiology. With technically adequate studies and experienced interpretation, the combination of plain radiology and directed CT scanning provides a false negative rate of less than 0.1%. The scan should include the entire vertebral body above and below the region of interest, as these must be undamaged for subsequent internal fixation.

Ligamentous Instability

Clearance of the spine in unconscious patients is limited by the lack of clinical information. The incidence of unstable spinal injury in adult, intubated trauma patients is around 10.2%. The incidence of unstable, occult spinal trauma (not visible on plain films is around 2.5%. The options for full clearance of cervical spine injury are:
  • Continue precautions until fully conscious
  • Magnetic Resonance Imaging
  • Dynamic Flexion-Extension Fluoroscopy
  • CT Scan whole cervical spine

Continue spinal precautions until fully conscious.

Where the patient is expected to regain full consciousness in the following 24-48 hours, patients can be nursed with full spinal precuations. Once the patient has returned to full consciousness, clinical examination can exclude significant ligamentous injury.
Prolonged spinal immobilisation in critically ill patients leads to decubitus ulcers and deep venous thromboses while compromising nursing care, respiratory support and the management of traumatic brain injury.
A semi-rigid collar is not necessary in the adequately sedated, ventilated patient, and may increase intracranial pressure in patients with traumatic brain injury.

Magnetic Resonance Imaging

MRI is extremely sensitive at detecting soft tissue injuries without stressing the cervical spine. However the significance of such injuries with regards to the clinical stability of the spine is not clear, and the number of false positive examinations is high. MRI of ventilated patients is a significant undertaking requiring special non-ferromagnetic equipment. However the increasing use of MRI for critically ill patients is making this equipment cheaper and more widely available. Possibly because of the difficulties associated with undertaking routine MRI scans in these patients, there have been few good studies on the use of MRI in clearing the cervical spine in unconscious patients.

Dynamic Flexion-Extension Fluoroscopy

Fluoroscopy Passive dynamic flexion/extension stressing of the cervical spine, performed by an experienced clinician, should reveal most significant ligamentous injuries. Several centres have reported their results, and some guidelines give primary support to the use of dynamic fluoroscopy in clearance of the spine in unconscious patients.
However, there are significant difficulties in performing flexion/extension imaging routinely on the intensive care unit, and many spinal surgeons are unwilling to perform the study due to safety & resource implications. Of 625 patients currently reported in the literature, dynamic fluoroscopy has a sensitivity of 92.3% and specificity of 98.8%. Two cases of neurological deterioration during the study have been reported, including one complete quadriplegia.

CT Scan whole Cervical Spine

In recent years, the concept of full cervical spine CT for assessment of spinal injury has emerged. There are several studies that have demonstrated the robustness of the full CT scan, with sagittal and coronal reconstructions, for the exclusion of significant spinal injury. Widening, slippage or rotational abnormalities of the cervical vertebrae suggest soft tissue injury. An absence of such signs appears to exclude significant instability. Abnormal findings on the CT scan are evaluated by a spinal surgeon and additional modalities, such as MRI, can be employed. No study has missed a cervical spine injury, and no study has identified an injury on plain films that was not apparent on the CT scan.
Helical or multislice CT scanning from the Occiput to T1 is performed at 2-3mm collimation and 1.5mm pitch. Sagittal and coronal reconstructions are must be closely examined for indications of ligamentous instability. When whole cervical spine CT scanning is performed, the antero-posterior plain film becomes redundant.

Thoracic & Lumbar Spine Injury

  1. Thoracolumbar spine imaging is indicated if there is pain, bruising, swelling, deformity or abnormal neurology attributable to the thoracic or lumbar spinal regions.
  2. The presence of a fracture anywhere in the spine mandates full spinal imaging.
  3. Unconscious patients who cannot be assessed clinically also require radiological clearance of the whole spine.
The standard imaging for the thoracic and lumbar spine are antero-posterior and lateral radiographs.
CT scanning is carried out for any abnormal, suspicious or inadequately visualised ares. The scan should include the entire vertebral body above and below the level of injury, as these need to be uninjured if used for operative fixation.
Patients with abnormal neurology attributable to the thoracic or lumbar spine should undergo an MRI scan to visualise the spinal cord.

Paediatric Spine Injury

  1. Spinal evaluation in the paediatric population is similar to those in adults.
  2. Clinical and radiological evaluation of the immature anatomy requires particular care, with attention paid to X-ray variants.
  3. Spinal cord injury without radiographic plain film abnormality is more common in this age group and a thorough neurological examination is important.

Immobilization

Children have a disproportionately larger head size than adults, and when supine on a firm surface will be in a position of slight flexion. This slight degree of flexion is rarely a problem, though it can give rise to difficulties in X-ray interpretation. This can be corrected by placing a folded towel or sheet under the patient's shoulders to bring the cervical spine into the neutral position.
It may be difficult to immobilize a child adequately. Distress and discomfort may require that manual in-line stabilization is used instead of a semi-rigid collar, blocks and tape. Collar sizing may be difficult and there are no collars that adequately fit infants aged 6 and below.

Clinical Clearance

Clinical clearance of the spine is less well established in the paediatric population. While the NEXUS study (Vicellio) has shown promise in this area, of 3065 patients there were only 4 cervical spine injuries in patients under 9 years of age, and none below 2 years old.

Radiology

The immature anatomy of the paediatric cervical spine requires some expertise and familiarity to interpret and to avoid missed injuries. Due to the paediatric patients' larger head size, pseudosubluxation of C2 on C3, and anterior translations may appear as injuries rather than as consequences of mild flexion.

Antenatal Diagnosis of Orthopaedic Conditions

Antenatal Diagnosis of Orthopaedic Conditions:

Diagnostic methods to detect foetal malformatiions—due to chromosomal or
environmental defects—detection of neonatal musculoskeletal defects by history taking, Apgar score,
clinical examination and anthropometric measurement.
A foetus grows within the mother’s womb in a definite pattern. Any change in this pattern will lead to
congenital malformation. The change may be due to a change in the uterine environment or due to
chromosomal defect. The limbs start growing from the 5th to 6th week of intrauterine life. Changes which develop prior to this period is due to chromosomal abnormality. The changes which take place after that period are due to environmental defect.
Therefore, to diagnose any congenital malformation in the antenatal period needs a detail maternal
history taking which includes age of the patient, intake of different medicines, presence of diabetes,
suffering of the mother from any infection during pregnancy, any trauma during pregnancy, maternal or foetal problems, if any, in the previous pregnancy. The assessment of foetal growth is done as it happens in three phases—the first 12 weeks of organogenesis, the next phase from 13 to 28 weeks and the third phase from 28 weeks onward upto 40 weeks when the foetus grows upto its fullest development. Various congenital malformations occur due to intake of drugs life thalidomide, as it happened in UK and also from maternal suffering from diabetes or infections like measles. Any defect anticipated from history should be corroborated by foetal diagnostic tests like amniocentesis, ultrasonography and others.
The intake of different medicines which cause foetal malformation are aminopterin, thalidomide
(not used now-a-days), trimethadione, paramethadione and antibiotics like chloramphenicol and
tetracycline. The latter causes retarded skeletal growth, hypoplasia of enamel and pigmentation of teeth.
Various diagnostic methods used to detect intrauterine foetal orthopaedic conditions are:
i. Amniography—to diagnose meningomyelocele
ii. Ultrasonography in the third trimester to diagnose cranial malformations and gestational age
iii. Amniocentesis for cytogenetic studies on foetus
iv. Chorionic venous sampling to detect Down syndrome and the like, and rarely X-ray examination (not
in the first-two trimester) to know about bone dysplasias, skeletal malformation and fractures.
Detection of Musculoskeletal Abnormalities in the Neonatal Period
When an orthopaedic surgeon is asked to examine a newborn baby to detect the presence of any
orthopaedic problem, the methods he should follow are:
1. To obtain a thorough history, which encompasses
i. Antenatal history
ii. Natal history
iii. Neonatal history
iv. Family
v. Post-natal history
2. To find out intrauterine growth retardation.
3. To follow Apgar score for properly assessing the newborn.
4. Thorough examination of the baby.
5. Recording anthropometric measurements of the newborn.
Neonatal History Taking
a. Antenatal history: Should include obstetric history, maternal illness during or before pregnancy,
maternal drug intake during pregnancy, history of diabetes, oligo or polyhydramnios, intranatal
and post-natal history, to know notable intrapartum procedures like breech presentation or forceps
delivery.
Extremes of age during first pregnancy have some adverse effects. Maternal ages below 18
years and above 35 years are often associated with (i) Pre-term babies, (ii) Down syndrome and
(iii) Chromosomal anomalies.
Effects of some of the medicines consumed by the mother during early part of pregnancy have
been emphasised for a long-time, specially their deleterious effects on limb formation. Malformations
have been noted with the ingestion of phenytoin sodium, antimalarials and sodium valproate, the
last named drug is suggestive of producing spina bifida.
Diabetic mothers may have babies with vertebral anomalies, femoral hypoplasia and caudal
regression syndrome.
Increased or decreased quantity of amniotic fluid may produce some defects in the babies like
foetal limb defects and club foot from oligohydramnios; Down syndrome, Klippel Feil syndrome,
acondroplasia, multiple congenital anomalies syndromes and anencephaly from polyhydramnios.
Breech presentation—Many of the neonatal problems are caused by unusual presentation of the
baby at birth. About 3 per cent of babies, who are born by breech presentation have some foetal and
maternal factors as the cause. Orthopaedic problems like congenital dislocation of hip, myotonic
dystrophy, Down syndrome, hydrocephalus are some of the important foetal factors, whereas oligo
or polyhydramnios, uterine abnormalities, abnormal placental implantation, twin pregnancy, low
birth weight of babies are some of the maternal factors found in breech presentation.
The effects of breech on new born causing orthopaedic problems are minor ones like haematoma
over thighs, soft tissue injuries and injuries to sternomastoid to major problems like cranial injury,
Erb’s or Klumpke’s palsy, fracture of long bones, spinal cord injury, congenital talipes equinovarus,
birth asphyxia and many others.
b. In searching for natal, neonatal, post-natal and family history the object will be to find out any
deviation from the normal. In obtaining family history, the most important point is pedigree study,
which may indicate a genetic disorder. An elderly primae may have a risk of delivering a baby with
Down syndrome, as an old father points to achondroplasia or Marfan syndrome. It is very important
to search for a number of siblings and deaths among siblings, abortions, intrauterine deaths, familial
illness like diabetes or infectious diseases like tuberculosis and parental consanguinity as a primary
offender before going for a detailed pedigree study in some relevant cases, where a genetic problem
is found in the family tree.
To Find Any Intrauterine Growth Retardation
When the birth weight is less than the 10th percentile for that particular gestational age, it is due
to intrauterine growth retardation and the babies born may show symmetrical retardation causing hypoplastic babies with diminished head size, shorter length and height but fairly adequate subcutaneous
fat, having increased risk of congenital anomalies. On the contrary an asymmetrically retarded growth
causes hypotrophic baby presenting with disproportionately reduced size with a relatively large sized
head and remarkably reduced subcutaneous fat having post-natal problems of asphyxia, hypoglycaemia,
malnutrition and massive pulmonary haemorrhage.
To Follow Apgar Score for Properly Assessing the Newborn
Virginia Apgar1 in 1953 used this score to systematically assess birth asphyxia. She graded five clinical
features at one minute of birth of the baby with scoring from 0 to 2. Recently the assessment is done upto
20 minutes at intervals of 5 minutes. The parameters taken are heart rate, respiratory effort, muscle tone,
response to catheter in the nostril, and colour of the skin. False positive results are possible in cases of
congenital myopathy or congenital neuropathy or acute cerebral trauma or spinal cord trauma with no
foetal asphyxia and low Apgar. A total score of 10 Apgar indicates best possible condition of the infant.
A score of 0 to 3 points towards immediate resuscitation of the infant.
Thorough Examination of the Baby
Orthopaedic examinations are not too many. But while doing so, any other obvious deformity like cleft lip
or palate is noted and written in the history sheet.
There are some important points followed while examining newborns:
i. The examination is done one hour after feeding
ii. The examination should be done gently, methodically and in the presence of the mother
iii. Those examinations which require quietness of the child are to be done first (e.g. auscultation of
heart and palpation of abdomen).
The orthopaedic surgeons are usually asked by paediatricians to see a newborn after common
life-threatening congenital anomalies like tracheo-oesophageal fistula, diaphragmatic hernia, ductal
dependent congenital heart disease, along with others like retarded mental development and growth,
genital hypoplasia, ear anomalies, neural tube defects like meningocele and encephalocele, renal
agenesis with associated urinary and pulmonary problems, obvious umbilical, gastric and intestinal
problems have been diagnosed by paediatric general surgeon.
Recognition of birth trauma is done carefully and systematically starting from head and neck for the
presence of cephalhaematoma, catput succedaneum, skull fractures, sternomastoid tumour, mandibular
fracture, brachial plexus injury, clavicle, humerus or femur fractures, presence of any petechiae or bruise,
and for any visceral injury in case of severe trauma.
Anthropometric Measurements in the Newborn
Anthropometric measurements in the newborn are done as follows:
i. Birth weight—weight recorded within one hour of birth
ii. Length from crown to heel preferably with the help of an infantometer
iii. Head circumference
iv. Mid arm circumference.
In the second examination, which should be done within 24 hours of birth, and the baby having been
fed one hour before the examination, a paediatric orthopaedic surgeon has to find out neuromuscular
maturity by noting posture—of universal flexion, lack or excess of it; hypertonicity shows excessive
flexion and hypotonicity showing lack of it. Some of the important reflexes are tested then.
Moro’s reflex is tested by raising the head of supine infant and allowing it to drop by 10° on to the
examiner’s supporting hand or alternatively by holding the baby at an angle of 45° from the cot and
then suddenly let the head fall back slightly into the palm. This reflex is not well-demonstrated in premature babies. Positive reflex shows opening of hands, extreme abduction of arms and hyperextension
of spine, followed by anterior flexion and adduction of arm are shown in babies born at or after 32 weeks.
Asymmetrical Moro’s reflex is found in Erb’s palsy, fracture clavicle or humerus and in hemiplegia.
Asymmetric tonic neck reflex: This simple test is done by rotation of the head to one side and
maintaining upto the count of five and doing the same to the opposite side. A position reflex with
extension of the upper limb on the side to which face is rotated with flexion of the arm on the side of
the occiput having less similar participation of the lower limbs are present from 35 weeks onwards.
Exaggerated reflex is a sign of cerebral injury.2 The above two reflexes disappear at 4 to 6 months of age of
the baby but may persist in cerebral palsy.
Search should then be made for Congenital Malformations
The malformations may occur in minor or major forms. Abnormalities in minor form of orthopaedic
interest are comptodactyly of fifth fingers, Potter’s thumb, syndactyly of second and third toes, short
fourth metatarsals, infantile bow leg, spooned nails.
Major malformations of common occurrence are musculoskeletal defects like club coot,
arthrogryposis, Down syndrome, limb reduction defects, CNS defects like anencephaly, spina bifida,
encepalocele, hydrocephaly and microcephaly.
Defects like congenital dislocation of hip or knee, radial club hand, amniotic bands should also be
looked for. Proper clinical examinations are done, if any condition is found.
Final Examination of the Baby at the Time of Discharge from the Hospital
This examination will confirm the presence of any abnormality in the baby or detect any, which has been
missed in the first examination. The treatment, if not advised before, should be given and the follow-up
intervals are informed. CNS abnormalities, if any, are confirmed by re-examination.
References
1. Apgar V. A proposal for new method for evaluation of the newborn infant. Anesth. Analg 1953;32: 260.
2. Kulkarni ML. Manual of Neonatology. Jaypee Brothers Medical Publishers (P) Ltd. New Delhi, 72.