Vickie L. Baer

Is “transfusion-associated necrotizing enterocolitis” an authentic pathogenic entity?

BACKGROUND: Necrotizing enterocolitis (NEC) sometimes occurs after a transfusion, but it is unclear whether this is a chance association or cause and effect.

Necrotizing enterocolitis in term neonates: data from a multihospital health-care system

Objective:In the past 5½ years, 30 term or near-term neonates in the Intermountain Healthcare system developed necrotizing enterocolitis (NEC) Bells stage ⩾II. We sought to identify possible explanations for why these patients developed NEC, by comparing them with 5847 others that did not develop NEC, from the same hospitals and of the same gestational ages, cared for during the same 5½-year period.Study design:Data were collected from neonates admitted to any of the Intermountain Healthcare NICUs with a birth date from 1 January 2001 to 30 June 2006, and a gestational age >36 weeks. A variety of patient features and feeding practices were compared between those that did vs did not develop NEC.Result:Forty-one neonates >36 weeks gestation were listed in the discharge records as having NEC of Bells stage II or higher. However, on review of these 41 medical records, 11 were seen to have had NEC of Bells stage I, whereas the remaining 30 had radiographs and clinical courses indicative of Bells stage ⩾II. Those 30 formed the basis of this study. Twenty-eight of the 30 developed NEC after having been admitted to an NICU for some other reason; the other two developed NEC at home, within 2 days of being discharged from an NICU. The 30 that developed NEC were more likely than the 5847 that did not develop NEC, to have congenital heart disease (P=0.000), polycythemia (P=0.002), early-onset bacterial sepsis (P=0.004) or hypotension (P=0.017). All 30 received enteral feedings before NEC developed; 29 were fed either artificial formula or a mixture of formula and breast milk. The one that was exclusively fed human milk was fed human milk with added fortifier (24 cal/oz). The 30 that developed NEC were more likely to be fed formula exclusively (P=0.000). Seven of the 30 had a laparotomy for NEC; two of the seven had total bowel necrosis and support was withdrawn. The other five had perforations and bowel resections. The mortality rate was 13% (4/30).Conclusion:In our series, NEC among term or near-term neonates was exclusively a complication developing among patients already admitted to a NICU for some other reason. We speculate that the combination of reduced mesenteric perfusion and feeding with artificial formula were factors predisposing them to develop NEC.

Implementing a program to improve compliance with neonatal intensive care unit transfusion guidelines was accompanied by a reduction in transfusion rate: a pre-post analysis within a multihospital health care system.

BACKGROUND: We previously reported that in the year 2006, approximately 35% of the transfusions administered in the Intermountain Healthcare neonatal intensive care units (NICU) were noncompliant with our transfusion guidelines. In January 2009 we instituted an electronic NICU transfusion ordering and monitoring system as part of a new program to improve compliance with transfusion guidelines.

Severe Thrombocytopenia in the NICU

OBJECTIVE: Severe thrombocytopenia (platelets ≤ 50000/μL) in a NICU patient can have significant consequences; however, previous reports have not focused exclusively on NICU patients with counts this low. METHODS: We identified all patients with severe thrombocytopenia who were cared for in the Intermountain Healthcare level III NICUs from 2003–2007. RESULTS: Among 11281 NICU admissions, severe thrombocytopenia was identified in 273 (2.4%). Just over 30% of these presented in the first three days of life. Half presented by day 10, 75% by day 27, and 95% by day 100. The prevalence was inversely related to birth weight. Cutaneous bleeding was more common in patients with platelet counts of <20000/μL; however, no statistically significant correlation was found between platelet counts and pulmonary, gastrointestinal, or intraventricular bleeding. The most common explanations for severe thrombocytopenia were acquired varieties of consumptive thrombocytopenia. Platelet transfusions (median 5, range 0–76) were administered to 86% of the patients. No deaths were ascribed to exsanguinations. The mortality rate did not correlate with the lowest platelet count but was proportionate to the number of platelet transfusions. CONCLUSION: The prevalence of severe thrombocytopenia in the NICU is inversely proportional to birth weight and most cases are acquired consumptive thrombocytopenias. We speculate that very low platelet counts are a causal factor in cutaneous bleeding, but pulmonary, gastrointestinal, and intraventricular bleeding are less influenced by the platelet count and occur primarily from causes other than severe thrombocytopenia. The lowest platelet count does not predict the mortality rate but the number of platelet transfusions received does.

Testing platelet mass versus platelet count to guide platelet transfusions in the neonatal intensive care unit

BACKGROUND: Platelet (PLT) transfusions can bestow significant benefits but they also carry risks. This study sought a safe means of reducing PLT transfusions to neonatal intensive care unit (NICU) patients with thrombocytopenia by comparing two transfusion guidelines, one based on PLT count and the other on PLT mass (PLT count times mean PLT volume).

Do platelet transfusions in the NICU adversely affect survival? Analysis of 1600 thrombocytopenic neonates in a multihospital healthcare system

Objective:Several studies have indicated a correlation between the number of platelet transfusions received by newborn intensive care unit (NICU) patients and the mortality rate. The number of platelet transfusions might be a marker for level of illness, and thus predictive of mortality. However, an alternative hypothesis is that multiple platelet transfusions themselves are harmful in this population.Study Design:We evaluated data from all thrombocytopenic neonates cared for in the Intermountain Healthcare NICUs in the past 4 years, seeking associations between the lowest platelet count recorded, number of platelet transfusions received and mortality rate. We also conducted a sensitivity analysis to examine the hypothesis that platelet transfusions were responsible for some fraction of the mortality rate.Result:Transfusion and outcome data were examined from 1600 thrombocytopenic NICU patients. At any level of platelet count, some patients received platelet transfusions but others did not. However, at all levels of platelet count, those that received platelet transfusions had a higher mortality rate. Neonates not given any platelet transfusions had a mortality rate of 2%, those with 1 or 2 transfusions had a mortality rate of 11% (P<0.001); those with >10 had a mortality rate of 35% (P<0.001); and those with ⩾20 had a mortality rate of 50% (P<0.001). A sensitivity analysis suggested that the platelet transfusions themselves were very likely responsible for some fraction of the increasing mortality rate.Conclusion:The number of platelet transfusions administered in the NICU predicts the mortality rate. Some of this correlation is ascribable to unknown and unmeasured factors such as level of illness. However, the present data and the sensitivity analysis both suggest that some of this correlation is due to harmful effects of multiple platelet transfusions in this group of patients.

Among very-low-birth-weight neonates is red blood cell transfusion an independent risk factor for subsequently developing a severe intraventricular hemorrhage?

BACKGROUND: A severe intraventricular hemorrhage (IVH) in a preterm neonate can result in life‐long disabilities or death. Pathogenic mechanisms responsible for IVH are incompletely understood. We postulated that if the timing of a severe IVH could be approximated by serial ultrasound, potentially relevant antecedents could be identified.

Antecedents of Bell stage III necrotizing enterocolitis

Objective:New biopharmaceuticals hold promise for preventing or treating necrotizing enterocolitis. However, it is unclear whether any such biopharmaceutical that requires enteral administration could be administered using an ‘early-treatment’ paradigm. This study was undertaken to assess this issue based on data from every case of Bell stage III NEC cared for during the past 7 years at Intermountain Healthcare.Study Design:Patients with Bell stage III NEC were identified from electronic medical record repositories and the diagnosis was validated using operative reports. Electronic and paper records of each patient were then used to identify potential clinical and laboratory antecedents occurring within the 48 h period preceding the diagnosis of NEC.Result:One hundred eighteen patients had Stage III NEC. The earliest recognized antecedents were nonspecific for NEC (apnea/bradycardia, skin mottling and irritability). These were recorded at 2.8±2.1, 4.5±3.1 and 5.4±3.7 (mean±s.d.) hours, respectively, before NEC was diagnosed. The most commonly identified gastrointestinal antecedents were blood in the stools, increased abdominal girth and elevated pre-feeding gastric residuals or emesis. These were identified 2.0±1.9, 2.8±3.1 and 4.9±4.0 h before NEC was recognized. Thirty-eight percent had a blood transfusion (18±12 h) preceding the NEC. Tachycardia, tachypnea, hypotension and diarrhea were rarely identified as antecedents and no consistent laboratory antecedents were discovered.Conclusion:We judge that an ‘early treatment of NEC’ paradigm testing any pharmacological agent that must be administered enterally is not feasible. The first recognized antecedents of Bell stage III NEC are nonspecific for gastrointestinal pathology and insufficient time exists for dosing between the first gastrointestinal signs and placement of the gastric decompression tube.

Adherence to NICU transfusion guidelines: data from a multihospital healthcare system

Objective:We critically reviewed every NICU blood component transfusion (packed erythrocytes, platelets, frozen plasma (FP) and cryoprecipitate) administered during a one-year period. This was done to determine the proportion of transfusions given out of compliance with the Intermountain Healthcare transfusion guidelines, and to look for patterns of non-compliance that could be addressed by quality improvement measures.Study Design:A detailed review was made of every transfusion administered to patients with a date of birth of 1 January 2006 through 31 December 2006, in any of three level III, perinatal-center-associated NICUs within Intermountain Healthcare.Result:During 2006 the three NICUs cared for 1759 neonates. Seventeen percent of these received one or more (median 3) erythrocyte transfusions, 4% received one or more (median 3) platelet transfusions, 6% received one or more (median 1) FP infusions and 2% received cryoprecipitate (median 1 dose). Seventy percent of the erythrocyte transfusions were given in compliance with the guidelines, as were 69% of the platelet transfusions, 65% of the FP transfusions and 94% of the cryoprecipitate administrations. Patients who received large numbers of transfusions were more likely to receive transfusion that violated the guidelines. Forty-five percent of patients who received 1 to 3 transfusions received all transfusions within guidelines. However, only 18% of patients who received 4 to 10 transfusions received all within guidelines. No patient who received >10 transfusions received all within the guidelines. Erythrocyte transfusions given early in the hospital course were likely to be within guidelines; 72% (588/818) in the first 29 days were compliant with guidelines, but compliance fell to 61% (144/237) for transfusions administered after 29 days (P=0.002). About half of the platelet transfusions given early in the hospital course were in violation of guidelines, but after day 9, 83% of platelet transfusions were compliant with guidelines (P=0.000).Conclusion:Opportunities exist in our healthcare system to improve compliance with our transfusion guidelines. Such opportunities are greatest among neonates receiving multiple transfusions, among those receiving erythrocyte transfusions late in their NICU course and among those receiving platelet transfusions early in their NICU course.

Red blood cell transfusion of preterm neonates with a Grade 1 intraventricular hemorrhage is associated with extension to a Grade 3 or 4 hemorrhage

BACKGROUND: Some preterm infants with a Grade 1 intraventricular hemorrhage (IVH) are subsequently found to have a Grade 3 or 4 IVH, while in others the Grade 1 resolves without extending.