Sourabh Dutta

Early nasal intermittent positive pressure ventilation versus continuous positive airway pressure for respiratory distress syndrome

Aim:  To determine whether early nasal intermittent positive pressure ventilation (NIPPV), in comparison to early continuous positive airway pressure (CPAP), can reduce the need for intubation and mechanical ventilation in preterm neonates with suspected respiratory distress syndrome (RDS).

Adjunctive immunologic interventions in neonatal sepsis.

Because of inadequate sample sizes of randomized controlled trials, few immunologic interventions to treat or prevent neonatal sepsis have been reliably evaluated. International collaboration is essential in achieving timely, adequate samples to assess effects on mortality or disability-free survival reliably. Promising or possible therapeutic interventions in severe or gram-negative sepsis include exchange transfusions, pentoxifylline, and IgM-enriched intravenous immunoglobulin. Promising or possible prophylactic interventions include lactoferrin, with or without a probiotic; selenium; early curtailment of antibiotics after sterile cultures; breast milk; and earlier initiation of colostrum in high risk preterm infants. Prophylactic oral probiotics are safe and effective (P<.00001) in reducing all-cause mortality and necrotizing enterocolitis in preterm infants by over half, but do not reduce sepsis.

Predictive Clinical Scores for Diagnosis of Late Onset Neonatal Septicemia

There is a paucity of data regarding predictive values and likelihood ratios of clinical signs for the diagnosis of late onset neonatal septicemia. This study aimed to determine these parameters in a prospective fashion, deriving a score by combining the most useful signs and determining the diagnostic utility of the score. All neonates admitted to a neonatal unit over a 1-year period were monitored for the occurrence of 16 pre-defined clinical signs. Symptomatic episodes (105 episodes in 80 neonates) were investigated for sepsis, and diagnosed as definite sepsis (n = 30), most probable sepsis (n = 17), and no sepsis (n = 58). Seven clinical signs (grunting, abdominal distension, increased pre-feed aspirates, tachycardia, hyperthermia, chest retractions, and lethargy) had positive likelihood ratios (PLR) greater than 1, and were combined to make a composite score. When a weighted clinical score (WCS) was used to diagnose definite sepsis, a cut-off score of 2 gave the best positive predictive value (PPV) and PLR (52 per cent and 2.65, respectively), and a cut-off score of 1 gave the best negative predictive value (NPV) and negative likelihood ratio (NLR) (85 per cent and 0.44, respectively). A cut-off score of 2 had a PPV of 65 per cent for definite and/or probable sepsis. In conclusion, physicians who attempt to make a diagnosis of neonatal sepsis on purely clinical grounds can use a seven-item weighted clinical score.

Diagnosis of neonatal sepsis using universal primer polymerase chain reaction before and after starting antibiotic drug therapy.

OBJECTIVE To study universal primer 16S rRNA gene polymerase chain reaction (PCR) for diagnosis of blood culture-positive neonatal sepsis before and after starting antibiotic drug therapy. DESIGN Prospective study of diagnostic tests. SETTING Level III neonatal intensive care unit. Patients Neonates with a fresh episode of clinically suspected sepsis were enrolled; those with major malformations, life expectancy less than 12 hours, or contaminated blood cultures were excluded. INTERVENTIONS Before starting antibiotic drug therapy, PCR (0 hour), blood culture, and sepsis screening (complete blood cell counts, micro-erythrocyte sedimentation rate, and C-reactive protein level) were performed. The PCR was repeated 12, 24, and 48 hours after starting antibiotic drug therapy. MAIN OUTCOME MEASURES The primary outcomes were the sensitivity and specificity of 0-hour PCR for diagnosing blood culture-positive sepsis, and the secondary outcome was the proportion of 0-hour PCR-positive patients who remained positive after antibiotic drug therapy. RESULTS Of 306 patients evaluated, 242 were included (mean [SD] gestation, 32.2 [3.1] weeks; and mean [SD] birth weight, 1529.2 [597.2] g). Blood culture was positive in 52 patients and 0-hour PCR in 57. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of PCR were 96.2%, 96.3%, 87.7%, 98.8%, 26.1, and 0.04, respectively. Two patients were blood culture positive but 0-hour PCR negative, whereas 7 were 0-hour PCR positive but blood culture negative. Of the 0-hour PCR-positive patients, 7 remained positive at 12 hours and none at 24 and 48 hours after starting antibiotic drug therapy. In 0-hour PCR-positive patients, no predictors of positive 12-hour PCR were identified. CONCLUSION Universal primer PCR can accurately diagnose neonatal sepsis before but not after antibiotic drugs are given.

Intrapartum antibiotics and risk factors for early onset sepsis

Objective To determine the independent risk factors for early onset neonatal sepsis (EONS) in a setting where the policy is to use intrapartum antibiotic prophylaxis (IAP) for known risk factors. Design Prospective cohort study. Setting Level III neonatal unit in a developing country. Patients Consecutive mother–infant dyads (gestation ≤34 weeks) with no major neonatal malformations. Interventions Thirteen putative maternal and neonatal risk factors and use of IAP were assessed. Neonates were followed until 72 h of life for signs of EONS. Blood cultures were drawn on clinical suspicion of EONS and/or prior to starting prophylactic antibiotics for high risk asymptomatic neonates. Main outcome Culture-proven EONS (onset at <72 h). Results 601 mother–infant dyads were enrolled (mean (SD) gestation=31.8 (2) weeks; mean (SD) birth weight 1559.4 (452) g). The best fitted multivariable logistic regression model had six independent risk factors (adjusted OR (95% CI)): vaginal examinations ≥3 (9.5 (3 to 31)), clinical chorioamnionitis (8.8 (2 to 43)), birth weight <1500 g (2.8 (2 to 5)), male sex (2.7 (2 to 5)), gestation <30 weeks (2 (1 to 4)) and no IAP (2 (1.04 to 4)). Regression coefficients were converted into scores of 6, 6, 3, 3, 2 and 2, respectively. Internal prediction accuracy was 86.5% and c statistic was 0.75 (95% CI 0.70 to 0.81, p<0.001). Conclusions Vaginal examinations ≥3, clinical chorioamnionitis, birth weight <1500 g, male sex, gestation <30 weeks and no intrapartum antibiotics were independent risk factors for EONS among preterm infants of ≤34 weeks’ gestation.

Low plasma protein C values predict mortality in low birth weight neonates with septicemia.

Background: Septicemia activates coagulation and decreases activated protein C (APC). Low APC in adults is associated with multiorgan dysfunction and mortality, but such data in neonates are lacking. Being deficient in APC, neonates may be especially vulnerable to the effects of low APC. Methods: This cohort study was conducted on 40 neonates with severe bacterial septicemia to determine the relationship between plasma APC values and mortality, time to mortality, and hazard of dying. Low birth weight neonates with sepsis, organ dysfunction, and systemic inflammatory response syndrome were enrolled after parental consent. Plasma APC was assayed at enrollment and subjects were followed for 14 days from enrollment. Low birth weight neonates, who had major malformations, severe birth asphyxia, or received blood products before APC assay, were excluded. Primary outcome: comparison of APC level between survivors and nonsurvivors. Secondary outcomes: survival with low versus normal APC; and hazard ratio of APC, adjusted for birth weight, Score for Neonatal Acute Physiology and number of affected organs. Results: Forty of 74 eligible neonates were included. Twenty-five of the enrolled neonates died within 14 days. APC levels in nonsurvivors were lower than in survivors [median (interquartile range) %, 15 (4.5–21) versus 33 (18–55); P < 0.001]. Ten nonsurvivors versus 1 survivor had low APC (P = 0.03). Positive predictive value (PPV) of low APC values for mortality was 90.9%. Survival in the low APC group (n = 11) was shorter than in normal APC group [median (95% confidence interval) days, 3 (2.3–3.7) versus 10, P value <0.001]. APC value was independently associated with hazard of dying [adjusted risk 0.95 (95% confidence interval 0.92–0.99), P = 0.02]. Each 1% rise in APC decreased the hazard of dying by 5%. Conclusions: Mortality was higher and duration of survival shorter in septic neonates with lower plasma ACP. The latter was an independent predictor of the hazard of dying.

Selective head cooling after neonatal encephalopathy

responses more than it does favourable responses and that this influence could be absent in severe injuries. During intervention, this intuition could have introduced bias against patients with more severe abnormalities on amplitudeintegrated electroencephalography (aEEG). A post-hoc subgrouping and analysis might have controlled such potential bias. Taken as they stand, the data still reveal a potential 51% reduction in risk in the more compromised neonates (1·8, 0·49–6·4). This finding is quite reassuring considering that the right side of the risk (6·4-fold increase) is not inconsistent with the risk from no intervention. Overall, the result of the study suggests a potentially clinically important benefit of head cooling in neonatal hypoxic-ischaemic encephalopathy as a group, and could be of high clinical usefulness in developing economies where neonatal hypoxic-ischaemic encephalopathy is more common and where aEEG might not be available but head cooling could be feasible.

Use of eutectic mixture of local anesthetics in children

The Eutectic Mixture of Local Anesthetics (EMLA) is a topical application, which has proved to be a useful medication for providing pain relief among children. It is an emulsion containing a 1 : 1 mixture of lidocaine and prilocaine. The high concentration of the uncharged anesthetic base in the microdroplets of the emulsion ensure effective skin penetration. In the pediatric population EMLA has been shown to be efficacious when it is used prior to venipuncture, cannulation, lumbar puncture, laser treatment of port wine stains, curettage of molluscum contagiosum or vaccination. For several of these indications, the efficacy has been documented by double blind controlled trials, that have used objective and quasi-objective scales for assessing pain relief. The dose of EMLA is between 0.5 to 1 gram, and the cream should be applied half to one hour prior to the procedure. Local side effects are very mild, and the only systemic side effect of importance is the risk of methemoglobinemia in young infants. The literature has conflicting reports about the safety of EMLA in neonates.

Enalapril-induced acute renal failure in a newborn infant

Abstract.A full-term baby boy developed congestive cardiac failure secondary to left-to-right shunts. He developed acute renal failure following the administration of oral enalapril given for the treatment of cardiac failure. There was no underlying renal disease or renal artery stenosis. He required three peritoneal dialyses, following which he recovered from the renal failure.

Effect of delay in analysis on neonatal cerebrospinal fluid parameters

Objectives: The effect of delayed analysis on cerebrospinal fluid (CSF) white blood cell (WBC) count and glucose has never been studied in neonates. Design: Prospective cohort study. Setting: Level III newborn unit. Patients: Neonates undergoing lumbar puncture were enrolled after consent. CSF was analysed at baseline (30 minutes) for protein, WBC and glucose; and from the same sample for WBC and glucose after a lag of 2 h and 4 h after lumbar puncture. Those with traumatic/inadequate CSF were excluded. Subjects were classified in three groups (n  =  20 each) based on baseline WBC count: no WBC, 1–30 WBC and >30 WBC/μl. Analysis was by repeated-measures ANOVA. Results: There was a significant decline in mean (SD) CSF glucose from baseline to 2 h and 4 h (41.0 (19) to 38.3 (19) and 36.2 (20) mg/dl, respectively) and WBC count (36 (45) to 28.6 (38) and 23.8 (34) cells/μl, respectively; both p<0.001). CSF glucose and WBC declined in all three groups (p<0.001). High baseline CSF WBC (p<0.001) and protein (p<0.001) was associated with a more rapid decline in the levels of CSF WBC, but not glucose. True CSF parameters could be predicted from 4-h parameters: “baseline glucose 5.4 + 0.98 (4-h glucose)” (adjusted R2 97.2%, p<0.001) and “baseline WBC 1.3 (4-h WBC) +0.05 (protein)” (adjusted R2 98.8%, p<0.001). In group 3, a diagnosis of meningitis (based on pleocytosis) would be missed in 52.6% and 78.9% subjects at 2 h and 4 h, respectively. Conclusions: CSF WBC count and glucose decrease significantly with time. Reliance on WBC counts of delayed samples can result in underdiagnosis.