AIIMS protocol NICU 2010PGI Chandigarh Protocol NICU 2010Manual of neonatal care John P ClohertyAvery’s Disease of newborn 8th EditionForanoff & Martin Neonatal & perinatal medicine, Volume II 8th Edition
Neonatal sepsis is a clinical syndrome characterized by signs and symptoms ofinfection with or without accompanying bacteremia in the first month of life. Itinclude:-septicemia,meningitis,pneumonia,arthritis,osteomyelitis, andurinary tract infections.Superficial infections like conjunctivitis and oral thrush are not usually includedunder neonatal sepsis.
1. Low birth weight (<2500 grams) or prematurity2. Febrile illness in the mother with evidence of bacterial infection within 2 weeks prior to delivery.3. Foul smelling and/or meconium stained liquor.4. Rupture of membranes >24 hours.5. Single unclean or > 3 sterile vaginal examination(s) during labor6. Prolonged labor (sum of 1st and 2nd stage of labor > 24 hrs)7. Perinatal asphyxia (Apgar score <4 at 1 minute)Presence of foul smelling liquor or three of the above mentioned risk factors warrant initiation of antibiotic treatment. Infants with two risk factors should be investigated and then treated accordingly.
Neonates who become symptomatic after 72 h must be evaluated for LOS.. Based on clinical assessment the neonate must be categorized into low probability of sepsis or high probability of sepsis. “Low probability” represents situations where the clinician would be willing to withhold antibiotics if-the sepsis screen is negative. Those with low probability of sepsis (e.g. single episode of apnea, but otherwise well) should undergo a sepsis screen. The purpose of the sepsis screen is to rule out sepsis rather than to rule in sepsis. The sepsis screen consists of:TLC, CRP, ANC. ITR and micro-erythrocyte sedimentation rate (m-ESR).
Components Abnormal valuesTotal leukocyte count <5000/mm3Absolute neutrophil count <1750/mm3Immature /total neutrophil >0.2Micro-ESR >10 mm in 1st hourC reactive protein (CRP) >1mg/dLo CRP: It is done by quantitative ELISA or by a bedside semi- quantitative latex agglutination kit. More than 1 mg/dL is positive.o ANC: It must be read off Manroe’s charts, Schelonka’s chart or Mouzinho’s chart, depending on whether it is a term baby or a preterm baby respectiveIy.
o ITR: It is considered to be positive if>20%. ITR is defined as Immature PMN (band forms, metamyelo & myelocytes) Mature + immature neutrophilsMature neutrophil Band cell 12
o mESR, Value (in mm in first hour)> “3+age in days” in the 1 wk of life or >10 thereafter is considered positive. Two systematic reviews on sepsis screens reached the same conclusions- that there is no ideal test or combination of tests. Among the various tests, quantitative CRP is the best, followed by qualitative CRP and ITR. If all the parameters of the sepsis screen are negative in a neonate assessed to have low probability of LOS, antibiotics may not be started and the neonate must be monitored clinically. The screen must be repeated after 12-24h. Two consecutive completely negative screens are suggestive of no sepsis.
Since CRP is the key parameter in the sepsis screen, a pragmatic approach is that if the CRP alone is positive or any two parameters of the sepsis screen are positive, a blood culture must be drawn and empirical antibiotics must be started. A CSF examination must be performed. Neonates assessed to have a high clinical probability of sepsis may not be subjected to a sepsis screen, because a negative screen would not alter the decision to start antibiotics. A CSF examination must be performed.
Sepsis screenBlood cultureLP Revised guideline for empirical treatment of meningitis based on csf parameter Among neonates with Among neonates with suspected sepsis blood culture proven sepsis Preterm babies •WBC >25 AND protein >170 •WBC >10 OR • OR •WBC>100 •Glucose <25 Cut-off values to •OR OR diagnose meningitis •Glucose <25 •Protein >170 Term babies •WBC >21 •WBC >8 OR • OR •Glucose <20 OR •Glucose <20 •Protein >120
First line: Ciprofloxacin + Amikacin (covers - 75% isolates) . If meningitis is suspected, replace Ciprofloxacin. by Cefotaxime- sulbactam (see section D24) Second line: Vancomycin + Piperacillin-Tazobactam (covers - 90% isolates) Third line: Vancomycin + Meropenem (covers - 95-100%)The antibiotic policy is reviewed periodically and may change afterthe next review. Cephalosporins rapidly induce the production ofextended spectrum b-lactamases, cephalosporinases and fungalcolonization, and hence, are best avoided as empirical antibiotics.
Empirical upgradation must be done if the expected clinical improvement with the ongoing line of antibiotics does not occur. A minimum of 48-72 h of observation should be allowed before declaring the particular line as having failed. The duration may be longer for Vancomycin compared to the Penicillin group and Aminoglycosides In case the neonate is extremely sick or deteriorating very rapidly and the treating team feels that the neonate may not able to survive 48 h in the absence of appropriate antibiotics, a decision may be taken to bypass the first line of antibiotics and start with the second- line of antibiotics
If the growth is a non-contaminant, the antibiotic sensitivity must be assessed to decide whether antibiotics need to be changed or not. The following guidelines must be adhered to: o If the organism is sensitive to an antibiotic with a narrower spectrum or lower cost, therapy must be changed to such an antibiotic, even if the neonate was improving with the empirical antibiotics. o If possible, a single sensitive antibiotic must be used, the exception being Pseudomonas for which 2 sensitive antibiotics must be used. Two sensitive antibiotics (a Penicillin + an Aminoglycoside) may also be used for S aureus and E. fecalis.
o If the empirical antibiotics are reported sensitive, but the neonate has worsened on these antibiotics, it may be a case of in vitro resistance. Antibiotics may be changed to an alternate sensitive antibiotic with the narrowest spectrum and lowest cost.o If the empirical antibiotics are reported resistant but the neonate has improved clinically, it may or may not be a case of in-vivo sensitivity. In such cases a careful assessment must be made before deciding on continuing with the empirical antibiotics. One must not continue with antibiotics with in vitro resistance in case of Pseudomonas, Kiebsiella and MRSA; and in cases of CNS infections and deep-seated infections.o If no antibiotic has been reported sensitive, but one or more has been reported moderate1y sensitive’, therapy must be changed to such antibiotics at the highest permissible dose. Use a combination, in such cases.
The survival of a sick septic newborn often depends uponaggressive supportive care. Oxygen saturation should be maintained in the normal range and mechanical ventilation may be required in case of increased work of breathing. Anemia, thrombocytopenia, and DIC are treated with appropriate transfusions. Packed red cells and FFP might have to be used. Septic infants should be screened for hypoglycemia and treated appropriately. Management of Septic Shock
IVIGThe currently available evidence does not support the useof IVIG. IVIG may be used in a difficult situation, afterdiscussion with the consultant.Dose : pentaglobin 5 mL/kg/d for 2 d (IgM 6 mg, IgA 6mg and IgG 38 mg/ml).Among patients with clinically suspected infection, thereduction of mortality with IVIG is of borderlinesignificance [typical RR 0.63 (95% CI; 0.40, 1.00)]. Incases of subsequently proven infection the reduciton inmortality is statistically but has very wide Cl [typical RR0.55 (95% Cl; 0.31, 0.98)].
Exchange transfusion (ET): Sadana et al have evaluated the roleof double volume exchange transfusion in septic neonates withsclerema and demonstrated a 50% reduction in sepsis relatedmortality in the treated group. We perform double-volumeexchange transfusion with cross-matched fresh whole blood asadjunctive therapy in septic neonates with sclerema..Granulocyte-Macrophage colony stimulating factor (GM-CSF):This mode of treatment is still experimental.
Prevention of infections Exclusive breastfeeding Keep cord dry Hand washing by care givers Hygiene of baby No unnecessary interventionsTeaching Aids: NNF NS- 26
Control of hospital infections Hand washing by all staff Isolation of infectious patient Use plenty of disposable items Avoid overcrowding Aseptic work culture Infection surveillanceTeaching Aids: NNF NS- 27
Work culture Sterile gowns and linen for babies Hand washing by all Regular cleaning of unit No sharing of baby belongings Dispose waste-products in separate binsTeaching Aids: NNF NS- 28
DefinitionDefined as total serum calcium concentration of <7 mg/dL or anionized calcium concentration of <4 mg/dL (i.e. 1 mEq/L).umbilical calcium level is 10-11mg/dLfirst 24-48h-7.5-8.5 mg/dL .Classification: early onset (<3 d) and late onset (>3 d)Causes:Early onset: Prematurity, 1DM, perinatal asphyxia, maternal intakeof anticonvulsants, IUGR. If hypocalcemia does not resolve within72 h of therapy investigate for causes of late onset hypocalcemia.
TreatmentMaintenance: 4-6 mL/kg/d of Ca gluconate IV (added in last 2 h of6 hourly IVF)Preparation: Ca-gluconate 10% (IV)- 9 mg/mL (preferred), Ca-chloride (IV)-27 mg/mLTherapeutic:Asymptomatic: increase maintenance to 8-12 mL/kg/d of Ca-gluconateSymptomatic: 2 mL/kg of Ca-gluconate diluted in 1:1 dilution withNS or 5% D IV over 10-15 mm under strict cardiac monitoring(stop infusion if HR drops for >20 beats/mm than baseline or anyother arrhythmia appears on ECO). Start maintenance calcium afterbolus dose.
Hypocalcemia Total serum Cal <7 mg/dl Asymptomatic 80 mg/kg/day for 48 hrs (8 mL/kg/day of 10% calcium gluconate ) Taper to 40 mg/kg/day for one day Then stop SymptomaticBolus of 2 mL/kg calcium gluconate 1:1 diluted with 5 % dextrose over 10 minutes under cardiac monitoring Followed by continuous infusion 80 mg/kg/day for 48 hrs (8 mL/kg/day of 10% calcium gluconate ) Document normal calcium at 48 hrs Then taper to 40 mg/kg/day for one day Then stop Prophylactic Preterm< 32 wks, sick IDM, severe asphyxia 40 mg/kg/day for 3 days (4ml/kg/day of 10% calcium gluconate ) IV or oral if can tolerate per oral Treatment is for 72 hours Continuous infusion is better than bolus Symptomatic babies treatment is 48 hrs continuous infusion
Prolonged or resistant hypocalcemiaThis condition should be considered in the following situations: Symptomatic hypocalcemia unresponsive to adequate doses of calcium therapy Infants needing calcium supplements beyond 72 hours of age Hypocalcemia presenting at the end of the first week. These infants should be investigated for causes of LNH
Causes of late onset hypocalcemia Increased phosphate load--Cow milk, renal insufficiency Hypomagnesemia Vitamin D deficiency Maternal vitamin D deficiency Malabsorption Renal insufficiency Hepatobiliary disease PTH resistence--Transient neonatal pseudohypoparathyroidism Hypoparathyroidism Primary Hypoplasia, aplasia of parathyroid glands - (Di George’s syndrome), CATCH 22 syndrome (cardiac anomaly, abnormal facies, thymic aplasia, cleft palate, hypocalcaemia with deletion on chromosome 22) Activating mutations of the calcium sensing receptor (CSR) Secondary Maternal hyperparathyroidism
Metabolic Syndromes Kenny-caffey syndrome Long-chain fatty acyl CoA dehydrogenase deficiency Kearns-sayre syndromeIatrogenic Citrated blood products Lipid infusions Bicrbonate therepy Diueretics (loop diuretics) Glucocorticosteriods Phosphate therepy Use of Aminoglycosides (mainly gentamicin) as single dose Alkalosis Phototherapy
Investigation required First line Second line Others Serum phosphate Serum magnesium CT brain for calcification Serum alkaline Serum parathormone Echocardiography phosphatase (SAP) levels (PTH) Vitamin D levels (1,25 Liver function tests Urine calcium creatinine D3) Renal function tests ratio Hearing evaluation X ray chest/ wrist Maternal calcium, Serum cortisol Arterial pH phosphate, and alkaline Thyroid function tests phosphataseS.No. Disorder causing Findings hypocalcemia1 Hypoparathyroidism High : Phosphate Low : SAP, PTH, 1,25 D32 Pseudo High : SAP, PTH, Phosphate Hypoparathyroidim Low : 1,25 D33 Chronic renal failure High : phosphate, SAP, PTH, pH (acidotic), deranged RFT Low : 1,25 D34 Hypomagnesemia High : PTH Low : Phosphate, Mg,1,25 D35 VDDR1 High : SAP, PTH Low : Phosphate, 1,25 D36 VDDR2 High : SAP, 1, 25 D3, PTH Low : Phosphate
Treatment of LNHThe treatment of LNH is specific to etiology and may in certaindiseases be lifelong.1. Hypomagnesemia: Symptomatic hypocalcemia unresponsive toadequate doses of IV calcium therapy is usually due tohypomagnesemia. It may present either as ENH or later as LNH.The neonate should receive 2 doses of 0.2 mL/kg of 50% MgSO4injection, 12 hours apart, deep IM followed by a maintenance doseof 0.2 mL/kg/day of 50% MgSO4, PO for 3 days.2. High phosphate load: These infants have hyperphosphatemiawith near normal calcium levels. Exclusive breast-feeding shouldbe encouraged and top feeding with cow’s milk should bediscontinued. Phosphate binding gels should be avoided.
Treatment of LNH3. Hypoparathyroidism: These infants tend to behyperphosphatemic and hypocalcemic with normal renal function.Elevated phosphate levels in the absence of exogenous phosphateload (cow’s milk) and presence of normal renal functions indicatesparathormone inefficiency. It is important to realize that if thephosphate level is very high, then adding calcium will lead tocalcium deposition and tissue damage. Thus attempts should bemade to reduce the phosphate (so as to keep the calcium and thephosphate product less than 55). These neonates needsupplementation with calcium (50 mg/kg/day in 3 divided doses)and 1,25(OH)2 Vitamin D3 (0.5-1 mg/day). Syrups with 125 mgand 250 mg per 5ml of calcium are available.1,25(OH)2 vitaminD3 (calcitriol) is available as 0.25 mg capsules. Therapy may bestopped in hypocalcemia secondary to maternalhyperparathyroidism after 6 weeks.
Treatment of LNH4. Vitamin D deficiency states: These babies have hypocalcemiaassociated with hypophosphatemia due to an intact parathormoneresponse on the kidneys. They benefit from Vitamin D3supplementation in a dose of 30-60 ng/kg/dayMonitoringThe baby is monitored for the SCa, and phosphate, 24 hour urinarycalcium, and calcium creatinine ratio. Try to keep the calcium inthe lower range as defective distal tubular absorption leads tohypercalciuria and nephrocalcinosis.
Treatment of LNHPrognosis and outcomeMost cases of early neonatal hypocalcemia resolve within 48-72hours without any clinically significant sequelae.Late neonatal hypocalcemia secondary to exogenous phosphateload and magnesium deficiency also responds well to phosphaterestriction and magnesium repletion. When caused byhypoparathyroidism, hypocalcemia requires continued therapy withvitamin D metabolites and calcium salts. The period of therapydepends on the nature of the hypoparathyroidism which can betransient, last several weeks to months, or be permanent.
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