Prevention of IVH
Many trials and prevention strategies were based on the general theory that the incidence of IVH would decrease if episodes of cerebral blood flow fluctuations, hypoxia, hypercapnia, and increased venous pressure could be minimized in the fetus and infant.
- Prenatal elimination of stress to fetus: Prenatal strategies focus on the elimination of any stress condition by optimal obstetric management and a smooth delivery, judicious usage of caesarean section, and administration of steroids and vitamin K (18).
- Postnatal modulation in blood flow and bleeding: Postnatal approaches are almost exclusively pharmacological prevention strategies. Agents designed to modulate cerebral blood flow to the preterm brain may alter other developing organs or impair neurogenesis, and cautious administration of them is mandatory (57).
- Phenobarbital ineffective: Phenobarbital was believed to have a neuroprotective effect by decreasing the metabolic rate of cerebral tissue, inhibiting seizures, and stabilizing blood pressure and production of free radicals. Antenatal administration failed to reduce IVH, while postnatal administration could not be recommended for prevention of IVH. Additionally, phenobarbital was found to increase risk for requiring mechanical ventilation (86, 104, 111).
- Steroid stabilization of germinal matrix: Steroids are used routinely before delivery of premature infants, primarily to support respiratory function of the newborn. However, it was found that with their use, the incidence and severity of IVH were also decreased. Further studies demonstrated that this effect was due not only to a reduction of perinatal respiratory distress but also directly to potential stabilization of germinal matrix microvasculature (23, 50, 59).
- Indomethacin lowers IVH: Indomethacin is an anti-inflammatory agent used in preterm infants to close patent ductus arteriosus and prevent IVH. Trials have shown that it decreases the rate and severity of hemorrhage in the newborn by inhibition of COX-1 and COX-2 isoforms and also decreases prostaglandin synthesis, possibly resulting in maturation of the basement membrane, improvement in autoregulation, and stabilization of the blood-brain barrier. Indomethacin is associated with increased risk of intestinal perforation, and controversy remains about its long-term effects on neurodevelopmental outcome. Indomethacin protection against IVH has been found more profound in male infants, and that finding suggests that gender is an important issue in infantile IVH (32, 61, 62, 95).
- Recombinant activated factor VII promotes hemostasis: Factor VII is a hemostatic agent used to treat patients with hemophilia and other bleeding disorders such as major trauma, oral anticoagulation, and liver dysfunction. When administered, it binds to activated platelets and promotes generous thrombin formation and further hemostasis. Small case series involving the administration of activated factor VII to neonates showed appropriate safety and effectiveness, and the use of factor VII deserves further investigation (7, 26, 64).
- Other agents found to be ineffective: Ethamsylate, ibuprofen, vitamin E, and pancuronium have been studied but have not been found to prevent IVH in neonates and have limited use in current practice.
Intervention for Preterm Infants
Serial lumbar punctures
- Temporizing procedure: Although this is a favored management technique by many, there is strong evidence that it fails to decrease the numbers of shunt operations, disabled infants, and deaths. Its routine use cannot be recommended, but in selected cases it could be useful in temporizing progressive hydrocephalus (105).
- 10–20 ml daily for several weeks: At least 10–20 ml of CSF must be removed at each tap on a daily basis for up to 3 consecutive weeks to be effective. The taps should be initiated as soon as possible. This time frame makes serial LPs rather strenuous both for the premature infants and for the treating doctor. Additionally, many infants cannot tolerate the longstanding lateral decubitus position required for the procedure. In clinical practice, after the first or second week LPs become less efficient at controlling ICP because an adequate volume of CSF becomes more difficult to remove (18).
- Communicating hydrocephalus and normal lumbar anatomy: For this technique to work, the hydrocephalus has to be communicating, and there cannot be any congenital anomalies affecting the area of the lumbar spine.
- Possible risk of infection: A trend towards increased CSF infection was noticed in addition to the discomfort of the procedure (105).
- Temporizing procedure: While a ventricular tap offers direct access to the ventricles and is easily performed free-handed or with ultrasound guidance, its overall impact in prevention of shunt operations and favorable outcome was not significant. Its use is limited as a short-term option in infants with rapid ventriculomegaly and when LPs are contraindicated (102).
- Risk of brain injury: Serial taps are avoided in most centers because of the repeated brain trauma and the risk of porencephaly (34).
External ventricular drainage
- Temporizing procedure: EVD is an accepted option to relieve rapidly the raised ICP and eliminate blood-filled CSF. Shunt dependency remains high (up to 65%) despite its use (14).
- Advantage of being physiological: EVD resembles the constant physiological drainage of CSF unlike the intermittent drainage offered by serial taps.
- Disadvantage of need for surgery and risk of infection and catheter dislodgment: In most centers the placement of an EVD requires transfer to the operating room, and that is not always feasible. EVD has serious disadvantages such as catheter dislodgement and high infection rates that increase over time. The rate of infection can exceed 50% after 3 weeks of continuous usage. Additionally, infections increase the rate of shunt dependency and progression to multiloculated hydrocephalus (16). Overall, almost all neonates with an EVD will require repeat operations for change of the ventricular catheter before they are ready for the definitive shunt.
Ventricular access devices
- Temporizing procedure: A ventricular access device or a subgaleal reservoir connected to a ventricular catheter is a reliable option for providing temporary access to CSF for intermittent removal of fluid. New, low-profile devices allow placement even in very-low-birth-weight infants and early commencement of CSF removal. It is preferable to drain smaller quantities of CSF (e.g., 10 ml/kg) daily rather than drain larger quantities less often. This approach is more physiological, and it avoids heavy drainage of CSF that can lead to electrolyte abnormalities. The frequency can be guided by clinical data (tension of anterior fontanelle, head circumference) and ultrasound measurements (VI) (16).
- Advantage of secured access to ventricles: Repeated penetration of brain parenchyma or lumbar dura is avoided, compared to ventricular taps and LPs. Infusion of intraventricular medication can be provided if needed.
- Disadvantage of requiring surgery, risk of skin erosion, and infection: Transfer to the operating room, skin erosion over the device, and intermittent control of ICP are disadvantages. Infection rates are 8–12% and remain an issue (35, 67).
- Temporizing procedure: This procedure is an alternative to a ventricular access device and will provide benefit for about 1 month according to those with experience using the technique. At the time of surgery a generous subgaleal pocket is created to allow free drainage of CSF (39).
- Disadvantage of large fluid accumulations under scalp: Large fluid collections can lead to scalp expansion, which later resolves. This can be cosmetically disfiguring and upsetting to the family and can obstruct the access to the anterior fontanelle for cranial ultrasonography. The infection rate for this technique may be lower than that for ventricular access devices (6%) (93).
Interventions for Older Infants
Interventions for preterm infants aim to stabilize progressive ventricular dilation to avoid on-going brain damage and allow time for weight gain, treatment of concomitant health problems, and strengthening of the immature immune system. If these interventions fail to control the progressive ventricular dilation, then the next and well-established treatment option is ventriculoperitoneal shunting. Criteria used to determine if such a shunt can be safely placed include:
- Sufficient body weight: Most authors cite the minimum acceptable weight for ventriculoperitoneal shunt insertion as >2000 g. Lower weights are associated with wound healing complications and higher infection rates. The abdominal cavity is more capable of absorbing CSF amounts (18).
- CSF protein less than 100 mg/dl: Higher protein levels as found in CSF samples were considered responsible for higher obstruction rates of the sophisticated valve mechanisms. The value of 100 mg/dl has been used as a cut off point, although many surgeons wouldn’t consider higher levels as a strong contraindication for ventriculoperitoneal shunt insertion (9).
- No active infection: Negative CSF cultures (ideally three consecutive samples, but one negative sample taken 3 days before the operation could suffice), low white cell count, low CRP (serum), and no evidence of remote infection (9) rule out active infection
- Abdominal cavity capable of handling CSF: There should be no evidence of abdominal infection or necrotizing enterocolitis and no recent intraabdominal operation or stoma.
Endoscopic third ventriculostomy
- Simple ETV not efficacious: A simple ETV is thought to be ineffective as an initial treatment of neonatal PHH due to the immaturity of the child’s brain and the blockage of CSF reabsorption sites by blood breakdown products (10, 68).
- ETV plus coagulation of choroid plexus(CPC) : This technique has been tried in infants with slowly progressing, communicating hydrocephalus. Two-thirds of infants have been reported to have stabilized (77). In a recent report on a small cohort of infants with PHH (previously shunted or not), a combination of ETV and coagulation of choroid plexus showed promising results, but only for those cases where the prepontine cistern was unobstructed (101).
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