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 INTRAVENOUS IMMUNE GLOBIN (IVIG) ADMINISTRATION IN NEONATES:

Patient population:

Neonates with isoimmune hemolytic disease of the newborn due to Rh or ABO incompatibility. Although data are limited, IVIG may be helpful in other types of Rh hemolytic disease such as anti-C and anti-E. It may be considered for non-isoimmune causes of hemolytic anemia such as G6PD deficiency.

Other indications for IVIG in neonates include immune thrombocytopenia and overwhelming sepsis.

Criteria for Use in Isoimmune Hemolytic Disease:

In Rh or ABO hemolytic disease, if the total serum bilirubin is rising despite intensive phototherapy or the total serum bilirubin level is within 2 to 3 mg/dL (34-51 μmol/L) of the exchange level.

Suggest guidelines from Hammerman 2000

Total Serum Billirubin (TSB) Levels for IVIG Administration in Term Healthy ABO-incompatible Coombs-positive Neonates.

AGE	TSB level despite 4 hours of phototherapy
<12 hours	204 mcmol/L (12 mg/dL)
12-24 hours	272 mcmol/L (16 mg/dL)
25-72 hours	306 mcmol/dL (18/dL)

 Additional Criteria: Hb<130 g/L

Consider administration as early as possible when active hemolytic disease of newborn is diagnosed and exchange transfusion is a possibility.

Intravenous gammaglobulin has been shown to reduce the need for exchange transfusion, repeat exchange transfusions, the duration of hospital stay, and phototherapy in Rh and ABO hemolytic disease. The mechanism of action appears to be related to blockage of Fc receptors in the neonatal reticuloendothelial system.

Contraindications

Neonates with IgA deficiency or hypogammaglobunemia (with IgA antibodies in the patient's serum)-risk of hypersensitivity or anaphylactic reactions .

Dosage and Administration:

Use Gamunex (10% Immune Globulin Intravenous (Human)), a ready-to-use sterile solution of human immune protein for intravenous administration.

Dose of 0.5 g-1.0 g/kg IVIG should be infused over 2 hours. If necessary, the dose can be repeated in 12 hours.

Sample Calculation

Gamunex is supplied in 2.5 g and 5g vials. To minimize wastage, choose the nearest vial size according to the patient's weight to administer within the range of 0.5-1.0 g/kg.

For 3 kg infant:

Dose of IVIG= 3kg x 1.0 g/kg= 3g (round to 2.5 g)

10% Solution has 1.0 g in 10 mL or 2.5 g in 25 mL

Infuse at 1.5 mL/hr (0.5 mL/kg/hr) x 30 minutes 

If tolerated, increase  to 12 mL/hr (4 mL/kg/hr) to infuse total volume approximately 2-2.5 hours.

For Gamunex, the maximum allowed rate of infusion is 8.4 mL/kg/hr

Gene X-pert system are slowly presenting in developing countries

 

GeneXpert MTB/RIF assay is a rapid diagnosis test of Tuberculosis (TB) and drug resistance. It is revolutionizing TB control with aids in prompt diagnosis and treatment (selection of appropriate TB regimen).

GeneXpert MTB/RIF assay is a nucleic acid amplification (NAA) test which simultaneously detects DNA of Mycobacterium tuberculosis complex (MTBC) and resistance to rifampin (RIF) (i.e. mutation of the rpoB gene) in less than 2 to 6 weeks for MTBC to grow and conventional drug resistance tests can add 3 more weeks.

This system integrates and automates sample processing, nucleic acid amplification, and detection of the target sequences.The primers in the XpertMTB/RIF assay amplify a portion of the rpoB gene containing the 81 base pair"core" region. The probes are able to differentiate between the conserved wild-type sequence and mutations in the core region that are associated with rifampicin resistance.The Centres for Disease and Prevention (CDC) recommends that NAA testing be performed on at least one respiratory specimen from patients who have a moderate or high suspicion of having pulmonary TB.

Background: Due to the emergence of Mycobacterium tuberculosis(M.tb) clinical isolates resistant to most potent first-line drugs (FLD), second-line drugs (SLD) are being prescribed more frequently. We explore the genetic characteristics and molecular mechanisms of M.tb isolates phenotypically resistant to SLD, including pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) isolates.

Methods : Drug-resistant (DR) M.tb isolates collected from 2012 to 2017 were tested using sequencing and phenotypic drug susceptibility testing. Genotypes were determined to explore their links with SLD resistance patterns.

Results: Of the 272 DR M.tb isolates, 6 non-multidrug resistant (non-MDR) isolates were fluroquinolones (FQ)-resistant, 3 were XDR and 16 were pre-XDR (14 resistant to FQ and 2 to second-line injectable drugs). The most frequent mutations in FQ-resistant and second-line injectable drugs resistant isolates harbored mutations conferring resistance to pyrazinamide. All XDR isolates belonged  to the Beijing genotype, of which one, named XDR+, was resistant to all drugs tested. One cluster including pre-XDR and XDR isolates was observed.

Conclusion: This is the first description of SLD resistance in Cambodia. The data suggest that the proportion of XDR and pre-XDR isolates remains low but is on the rise compared to previous reports. The characterization of the XDR+ isolate in a patient who refused treatment underlines the risk of transmission in the population. In addition, genotypic results show, as expected, that the Beijing family is the main involved in pre-XDR and XDR isolates and that the spread of the Beijing pre-XDR strain is capable of evolving into XDR strain. This study strongly indicates the need for rapid interventions in terms of diagnostic and treatment to prevent the spread of the pre-XDR and XDR strains and the emergence of more resistant one.

Head Injury

 Head Injury:

The study of the cause of death following head injury focuses attention on the important areas. The major cause of death is primary brain damage followed by multiple injuries, cerebral oedema and airway obstruction. These are the commonly recognized causes, the least common cause being intracranial haematomas .

Figure 17.1(a) CT brain scan showing raised intracranial pressure 

Pathophysiology of brain injury : 

The classical division of brain injury is into primary and secondary damage . This division is clinically useful. Primary brain damage occurs at the time of the injury, produces its clinical effect immediately and has proved resistant to most treatments. Secondary brain damage, on the other hand, occurs some time after the primary impact and is largely preventable and treatable. The importance of managing a head-injured patient is to recognize and document the primary brain damage and subsequently to prevent and treat secondary damage.

While traumatic brain injury results in an extraordinary cascade of neurochemical events, and there is much speculation as to its importance , most reasearch has focused on injuries to the axon, the neurone and the glia. While axonal injury considered to be irreversible with progressive changes in ultrastructure, the blood-brain barrier and neuronal function over time may provide some potential for treatment. While future treatment, currently the main emphasis remains on secondary brain damage which may begin very soon after the impact, necessitating important early management decisions.

Pressure/volume relationship:

The skull is a rigid compartment within which lies the brain, cerebrospinal flud (CSF), blood and extracellular fluid. The volume within the cranial vault is constant and any increase in volume results in an increase in ICP. The relationship between the pressure and volume is expressed in Figure 17.1. The major intracranial volumes are brain parenchyma (1200-1600ml), blood (100-150ml), and CSF (100-150ml). The latter two constitute about 20% of total intracranial volume and part of each is capable of rapid extracranial displacement. The initial increase in intracranial volume is catered for by the loss of CSF from the intracranial compartment, reduction in the amount of blood in the cerebrum followed by compression of brain tissue with herniation of the brain and a decrease in  CBF. The redistribution of the CSF and venous blood have little pathological consenquence but a reduction in CBF and the occurrence of brain herniation results in cerebral ischaemia and secondary cerebral damage.