Jw Davis

Therapeutic hypothermia delays the C-reactive protein response and suppresses white blood cell and platelet count in infants with neonatal encephalopathy

Background Therapeutic hypothermia (HT) delays the cytokine response in infants with neonatal encephalopathy (NE). Objective To determine if HT delayed the C-reactive protein (CRP) response and altered white blood cell (WBC), neutrophil and platelet count course during the first week of life in infants with NE. Design Retrospective cohort study. Setting Regional neonatal intensive care unit, UK. Patients 104 term infants with NE (38 normothermia (NT) and 66 HT) born between 1998 and 2010. Infants not exposed to prenatal sepsis risk factors were classified as group ‘A’ and exposed infants to group ‘B’. CRP >10 mg/L was defined as significant response. Main outcome measures Time to CRP >10 mg/L, peak CRP, WBC, neutrophil and platelet count. Results Blood cultures were negative in all the infants. In babies who had CRP response, HT delayed time to CRP >10 mg/L (median (95% CI): group A, HT: 36 h (28.3 to 48.0); NT: 24 h (0.0 to 24.0); p=0.001; group B, HT: 30 h (15.2 to 56.8); NT: 12 h (0.0 to 24.0); p=0.009) and time to peak CRP (median (95% CI): group A, HT: 60 h (60.0 to 72.0); NT: 36 h (0.0 to 48.0); p=0.001; group B, HT: 84 h (62.1 to 120.0); NT: 24 h (0.0 to 36.0); p=0.001). Compared with NT, HT was associated with reduction in slope of CRP elevation by 0.5 (95% CI 0.04 to 0.97), WBC by 2.18×109/L (95% CI 0.002 to 4.35) and platelet count by 32.3×109/L (95% CI 2.75 to 61.8) independent of exposure to sepsis risk, meconium aspiration and severity of asphyxia. Conclusions Therapeutic hypothermia delayed the initiation of CRP and its peak response, and depressed the WBC and platelet count compared with NT.

Human Parechovirus Infection in Neonatal Intensive Care

Background: Approximately 5–6% of all infective episodes in neonatal intensive care unit (NICU) are of viral origin. Previous studies suggest that human parechovirus (HPeV) infection presents most commonly in term infants, as a sepsis-like syndrome in which meningoencephalitis is prominent. Our aim was to study the infection rate and associated features of HPeV. Methods: Blood samples were taken from NICU babies older than 48 hours, who were being investigated for late onset sepsis. Clinical and laboratory data were collected at the time of the suspected sepsis episode. Samples were tested using universal primers and probe directed at the 5′-untranslated region of the HPeV genome by reverse transcriptase polymerase chain reaction (RT-PCR). Results were confirmed by electrophoresis and DNA sequencing. Results: HPeV was detected in 11 of 84 samples (13%). These infants had a mean [interquartile range (IQR)] gestational age of 28.9 (26.9–30.6) weeks and mean birth weight of 1.26 (SD = 0.72) kg. The median day of presentation was 16 (IQR: 11–27). These characteristics were similar to the infants without positive viral detection. Six infants presented with respiratory signs. One infant presented with signs of meningitis. Six of the 11 episodes of HPeV infection occurred during the winter months (December to February). No HPeV positive infants had abnormal findings on their 28-day cranial ultrasound examination. Conclusions: We found an HPeV infection rate of 13% in infants being tested for late onset sepsis. HPeV should be considered as a possible cause of sepsis-like symptoms in preterm infants.

The impact of a sepsis quality improvement project on neurodisability rates in very low birthweight infants

Objective Very low birthweight (VLBW; <1500 g) infants with late-onset sepsis (LOS) have an increased risk of neurodisability. Care bundles to reduce bloodstream infections in neonatal intensive care unit (NICU) are effective in reducing LOS. Our aim was to determine if a sepsis reduction bundle introduced through a quality improvement project would impact neurodevelopmental outcomes in VLBW infants. Design Cohort study. Setting Level 3 regional NICU in the South West of England. Patients VLBW infants born between 2002 and 2011. Interventions A sepsis reduction care bundle implemented between July 2006 and December 2007. Main outcome measures The primary outcome was risk of coagulase-negative Staphylococcus (CONS) infection diagnosed >3 days of age. Secondary outcomes were death and moderate cognitive impairment. A logistic regression model was derived using the birth era as the independent variable with adjustment for typical confounders. Results In total, 379 infants were born in the preintervention cohort and 378 in the postintervention cohort. The CONS infection rate was reduced after the intervention (26.7% vs 14.1% p<0.001). Death prior to discharge reduced without reaching statistical significance (14.1% vs10.9%, p=0.195). The rate of cognitive disability reduced in the postintervention cohort (18.8% vs 6.1%, p=0.042). The adjusted ORs (95% CI) for CONS infection, death and cognitive impairment were 0.46 (0.29 to 0.72), 0.73 (0.43 to 1.24) and 0.3 (0.07 to 1.33), respectively. Conclusions There appears to be an association between reduced cognitive disability and the implementation of a sepsis reduction bundle. Further study in larger series is required to confirm these findings.

Sedation management during therapeutic hypothermia for neonatal encephalopathy: Atropine premedication for endotracheal intubation causes a prolonged increase in heart rate☆

AIM Heart rate (HR) plays an important role in the assessment of stress during therapeutic hypothermia (TH) for neonatal encephalopathy; we aimed to quantify the effect on HR of endotracheal (ET) intubation and drugs given to facilitate it. If atropine premedication independently increased HR, the main indicator of effective sedation, we hypothesised that increased sedation would have been given. METHODS Thirty-two, term, neonates recruited into a randomised pilot study comparing TH and TH combined with 50% Xenon inhalation were studied. Indications for ET intubation included: resuscitation at delivery, clinical need and elective re-intubation with a cuffed ET tube if randomised to Xenon. Standard intubation drugs comprised one or more of intravenous morphine, atropine, and suxamethonium. Local cooling guidelines were followed including morphine infusion for sedation. RESULTS At postnatal hours five to eight atropine increased HR in a linear regression model (p<0.01). All other independent variables were excluded. Where more than one dose of atropine was given total morphine sedation given up to 8h into the treatment period was significantly higher (p<0.01). CONCLUSION We have shown that atropine premedication for ET intubation significantly increased HR, the main indicator of effective sedation and total morphine dose for sedation during early TH was increased where more than one dose of atropine was given. Bradycardia was not reported in any neonate, even without atropine premedication. We suggest that the use of atropine as part of standard premedication for ET intubation of term neonates undergoing TH should be reconsidered.

G211(P) Better cognitive outcomes for Very Low Birth Weight Infants after implementation of a sepsis reduction care bundle

Background Published data suggest that very low birth weight infants (VLBW; <1500 g) with late onset sepsis have increased risk of neurodisability. Care bundles to reduce blood stream infections in NICU have been shown to be effective. No studies have demonstrated the impact of these care bundles on long term neurodevelopmental outcome. Objective To determine if the implementation of a sepsis reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A sepsis improvement care bundle, based on the Vermont Oxford Network iNIQ package, was implemented in stages in a tertiary level NICU between 2006 and 2007. Mortality and neurological morbidity rates were compared for the pre-intervention (January 2001 to December 2007) and post-intervention (July 2008 to December 2012) periods. We excluded the 6 month period directly following full implementation of the intervention. The highest risk VLBW infants (<30 weeks’ gestation) had routine neurodevelopmental assessments at 24 months (corrected for gestation) using the Bayley Scales of Infant development (BSID). Moderate cognitive disability was defined as a cognitive/language score below 2SDs and moderate motor disability as a motor score below 2SDs. The outcome of cerebral palsy (CP) was assessed on neurological assessment at 2 years. Results Coagulase Negative Staphylococcus septicaemia rates were 7/1000 care days before implementation of the care bundle and from 2009, have reduced year on year to an average of 2.8/1000 care days by 2013. In the cohort of VLBW infants there was no significant reduction in mortality rates (66/426(16%) vs. 40/310(13%); p = 0.3). No significant difference was found in moderate motor disability (17/85(20%) vs. 3/42(7%); p = 0.07) or CP (10/94(11%) vs. 6/49(12%); p = 0.7), before and after the intervention. A significant reduction in moderate cognitive disability (16/86(19%) vs. 2/44(5%); p = 0.03) was found after full implementation of the sepsis care bundle. Potentially confounding variables (birth weight and gender) were not different (p > 0.05) in the pre and post intervention cohorts. Conclusions This is the first description of the long term impact of a sepsis improvement care bundle on neurodevelopmental outcomes in VLBW infants. The improvement seen in cognitive function at two years of age is likely to translate into significantly less long term learning disability.

G414(P) C-Reactive protein without sepsis after birth: Development of infant CRP nomograms

Background Early onset neonatal sepsis is an important cause of morbidity and mortality but remains a diagnostic challenge. C-reactive protein (CRP) is widely used to assist diagnosis of infection and monitor treatment response. CRP is synthesised by the liver in response to interleukin 6 within 6–8 h of tissue injury. Despite widespread use in infants with suspected sepsis, little is known about CRP responses after birth in the absence of infection. Objective To describe postnatal CRP responses in asymptomatic term and preterm infants with no evidence of infection Methods Data was collected from infants admitted to a tertiary NICU during two discrete time periods (Sept–Oct 2012; Apr–May 2013) who had blood taken for culture. CRP values and time from birth were recorded. Infants with symptoms of infection or a positive blood culture were excluded from analysis, as were those with congenital anomalies. Remaining infants were subdivided by gestational age. Normalised CRP curves were generated by linear interpolation between measured values, assuming CRP half-life of 18h. Individual subjects were ranked by CRP response and centile curves derived. Results 219 babies were screened in the study period. After exclusions, 85 infants (70 term, 15 preterm) remained. The median (range) birthweight and gestation were 3560 g (2080–4820 g) and 40+4 weeks (37–43) respectively in the term group and 1814 g (975–3020 g) and 34+2 weeks (27+5–36+4) in the preterm group. In asymptomatic term neonates, CRP peaked at 24 h of age, with the 75th centile 9.3 g/dL, 90th centile 21 g/dL, 95th centile 24 g/dL. In preterm babies, CRP peaked at 48 h, 90th centile=5 g/dL, 95th centile=19 g/dL. Excluding infants with risk factors for infection, 90th centile values remained raised in both groups. Conclusions We describe CRP centiles in infants without symptoms of infection in the first days after birth. A substantial proportion of uninfected term and preterm infants had raised CRP values, with more than 10% being sufficiently high (>10g/dL) to prompt further invasive investigations (current UK guidelines). We demonstrate raised CRP values, unrelated to infection, in a significant number of infants. Further characterisation of CRP responses in non-infected infants is needed to optimise use of this common test.

Performance of a Novel Molecular Method in the Diagnosis of Late-Onset Sepsis in Very Low Birth Weight Infants

Objective To compare the use of a generic molecular assay to ‘standard’ investigations used to assist the diagnosis of late onset bacterial sepsis in very low birth weight infants (VLBW, <1500g). Methods VLBW infants, greater than 48 hours of age, who were clinically suspected to have sepsis were investigated using standard tests (full blood count, C-reactive protein (at presentation) and blood culture), in addition, blood was taken for a universal molecular assay (16S rRNA reverse transcriptase PCR) for comparison. Clinical data were recorded during the suspected infection episode. A validated sepsis score (NEO-KISS) was used to retrospectively determine the presence of sepsis (independent of blood culture). The performance of each of the tests were compared by sensitivity, specificity, positive/negative likihood ratios (+/-LR) and postive/negative predictive values (PPV/NPV). Results Sixty-five babies with suspected clinical sepsis were prospectively included. The performance indicators are presented with 95% confidence limits. For the detection of bacteria, blood culture had sensitivity of 0.57 (0.34–0.78), specificity of 0.45 (0.30–0.61); +LR of 1.05 (0.66–1.66) and—LR of 0.94 (0.52–1.7); PPV of 33.3 (18.56–50.97) and NPV of 68.97 (49.17–87.72). Serum CRP had sensitivity of 0.92 (0.64–1) and specificity of 0.36 (0.17–0.59); +LR of 1.45 (1–2.1) and-LR of 0.21 (0.03–1.5); PPV of 44.46 (26.6–66.6) and NPV of 88.9 (51.8–99.7). The universal molecular assay had sensitivity of 0.76 (0.53–0.92), specificity of 0.95 (0.85–0.99); +LR of 16.8 (4.2–66.3) and-LR of 0.25 (0.1–0.5); PPV of 88.9 (65.3–98.6) and NPV of 89.4 (76.9–96.5). Conclusions In VLBW infants this universal molecular assay performed better in the diagnosis of late onset sepsis (LOS) than blood culture and CRP. Further development is required to explore and improve the performance of the assay in real-time diagnosis.

PS-214 Does A Total Sterile Collection Bundle Reduce False Positive Blood Culture Rates And Antibiotic Use In Neonatal Intensive Care?

Background and aim In neonatal intensive care coagulase negative Staphylococcus species can be both blood culture contaminant and pathogen. False positive cultures can result in clinical uncertainty and unnecessary antibiotic use. Our aim was to assess the effect of a total sterile blood culture collection bundle on the incidence of false positive blood cultures in a regional surgical neonatal intensive care unit. Method Clinical data of all infants who had blood cultures taken before and after the introduction of the collection bundle (sterile technique and 2% Chlorhexidine) were collected. The rates of false positive blood cultures, defined as the presence of a skin commensal and <3 predefined clinical signs (Modi et al. 2009), were compared. Results In total 367 blood cultures from 294 babies were assessed, 197 pre-intervention (PRE) and 170 following bundle introduction (POST). The median birth weight and gestation were similar in both groups. The rate of false positive cultures in the total PRE group was 9/197 (4.6%) compared to 1/170 (0.6%) in the POST group (p < 0.05). In infants <28 weeks’ the rates reduced from 4/29 (13.8%) to 0/30 (0%) (p < 0.05). Unnecessary antibiotic exposure rate was 7.7% in the PRE group versus 0.0% in the POST group (p < 0.05). Conclusion Implementation of this collection bundle reduced the number of false positive blood culture results. This has a potential benefit in reducing unnecessary antibiotic use and associated health care costs.

PC.44 Improved cognitive ability in preterm infants: The impact of a sepsis reduction care bundle

Background Very low birth weight infants (VLBW; <1500 g) with late onset sepsis have an increased risk of neurodisability. Care bundles to reduce blood stream infections in NICU have been shown to be effective. Objective To determine if the implementation of a sepsis reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A sepsis improvement care bundle was implemented in a tertiary level NICU between 2006–2007. Mortality and neurological morbidity rates were compared for the pre-intervention (January 2001–December 2007) and post-intervention (July 2008–December 2012) periods. The highest risk VLBW infants (<30 weeks’ gestation) had routine neurodevelopmental assessments at 24 months using the Bayley Scales of Infant development (BSID). Moderate cognitive disability was defined as a cognitive/language score below 2SDs. Results Coagulase Negative Staphylococcus septicaemia rates were 7/1000 care days before implementation of the care bundle and have reduced to an average of 2.8/1000 care days by 2013. In the cohort of VLBW infants there was no significant reduction in mortality rates (66/426(16%) vs. 40/310(13%); p = 0.3). A significant reduction in moderate cognitive disability (16/86(19%) vs. 2/44(5%); p = 0.03) was found after full implementation of the sepsis care bundle. Potentially confounding variables (birth weight and gender) were not different (p > 0.05) in the pre and post intervention cohorts. Conclusions This is the first description of the long term impact of a sepsis improvement care bundle on neurodevelopmental outcomes in VLBW infants. The improvement seen in cognitive function at 2 years is likely to translate into significantly less long term learning disability.

PS-215 Sepsis Reduction Care Bundles Improve Cognitive Outcome In Very Low Birth Weight Infants

Background Very low birth weight (VLBW) infants with late onset sepsis have increased risk of neurodisability. Care bundles to reduce these infections in NICU are effective. The impact of care bundles on long-term neurodevelopmental outcome has not been described. We aimed to determine if implementation of a sepsis-reduction care bundle was associated with improvement in neurodevelopmental outcomes in VLBW infants. Methods A multimodal sepsis improvement bundle was implemented in a regional NICU from July 2006. This bundle focused on hand hygiene and line care improvements. Mortality and neurological morbidity rates were compared pre- and post intervention (Jan ‘01 - Dec ‘07 vs. Jul ‘08 – Dec ‘12). Infants had neurodevelopmental assessment at 24 months corrected gestation with Bayley Scales of Infant development. Moderate cognitive disability was defined as a cognitive/language score below 2SDs, moderate motor disability as a motor score below 2SDs. Results Birth weight, gestation and gender were similar in both cohorts. Coagulase Negative Staphylococcus septicaemia rates reduced from 7/1000 care days before implementation to 2.8/1000 in 2012. Mortality rates were similar between the groups (66/426 vs. 40/310; p = 0.3). There was no difference in moderate motor disability (17/85 vs. 3/42; p = 0.07). There was a significant reduction in moderate cognitive disability (16/86 vs. 2/44; p = 0.03) after implementation of the sepsis care bundle. Conclusions Sepsis-reduction care bundles improve the 2-year neurodevelopmental outcome of VLBW infants. The improvement seen in cognitive function is likely to translate into significantly less long-term learning disability.