Transfusion related acute lung injury: a pediatric perspective

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality. TRALI occurs in children and adults, but the syndrome has not been reviewed from a pediatric perspective. We reviewed the literature on TRALI from a pediatric perspective. TRALI has been documented in pediatric patients, especially in the setting of hematologic malignancy. Additional TRALI cases have been reported in pediatric patients with a variety of diagnoses. TRALI is likely to be much more common than previously appreciated in the pediatric patient population. TRALI should be considered in the differential diagnosis of all pediatric patients who develop new acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) during or within six hours of a blood product transfusion. When a case of TRALI is suspected, a transfusion reaction report to the blood bank is important to initiate the investigation and identify the implicated donor.     

Choosing abdominal incision and closure techniques: a review

This review summarizes contemporary concepts of abdominal surgical incision creation and closure. The Ovid computerized database was searched for articles published in English from 1996 to 2003 using keywords pertaining to the specific topic of interest (e.g., suture, drain, surgical technique, fascia). Human prospective, randomized trials; meta-analyses; and evidence-based-focused reviews were assessed and data abstracted. Several earlier and animal-based studies on specific issues were included. The data indicate that: (1) the direction of the incision should be based upon obtaining adequate exposure; (2) hair should either be left in place or clipped at the time of surgery; (3) a single dose of prophylactic antibiotics should be given 30 minutes prior to surgery; (4) using a "deep" scalpel is unnecessary; (5) a scalpel and electrocautery are comparable for deepening the incision; (6) minimal peritoneal lavage with non-antibiotic containing solutions is adequate; (7) the peritoneum should not be routinely closed; (8) the fascia should be loosely approximated by a continuous mass closure using a slowly absorbable, monofilament suture with the smallest possible caliber and a suture:wound length ratio of at least 4:1; (9) retention sutures, subcutaenous sutures and drains do not appear to reduce the risk of wound complications; and (10) the skin may be closed in a variety of methods, but a semiocclusive dressing should be applied. As scientific evidence accumulates to refute traditional dogma, management of the surgical patient has undergone substantial changes. Surgeons should now be able to create and close an abdominal wound based upon sound scientific principles rather than simply "doing what I always do."     

Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory arrest

BACKGROUND: Glucocorticoids during cardiopulmonary bypass benefit pediatric patients undergoing repair of congenital heart defects and are routine therapy, but underlying mechanisms have not been fully examined. The hypothesis was that glucocorticoids could improve cardiopulmonary recovery after cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Crossbred piglets (5 to 7 kg) were cooled with cardiopulmonary bypass, followed by 120-min deep hypothermic circulatory arrest. Animals were then warmed to 38 degrees C, removed from bypass, and maintained for 120 min. Methylprednisolone (60 mg/kg) was administered in the cardiopulmonary bypass pump prime (intraoperative glucocorticoids) or 6 hours before bypass (30 mg/kg) in addition to the intraoperative dose (30 mg/kg; preoperative and intraoperative glucocorticoids). Controls (no glucocorticoids) received saline. RESULTS: Pulmonary vascular resistance in controls increased from a baseline of 152 +/- 40 to 364 +/- 29 dynes. s/cm(5) at 2 hours of recovery (p < 0.001). Intraoperative glucocorticoids did not alleviate the increase in pulmonary vascular resistance (301 +/- 55 dynes. s/cm(5) at 2 hours of recovery, p < 0.001). However, animals receiving pre and intraoperative glucocorticoids had no increase in pulmonary vascular resistance (155 +/- 54 dynes. s/cm(5)). Plasma endothelin-1 in controls increased from 1.3 +/- 0.2 at baseline to 9.9 +/- 2.0 pg/mL at 2 hours recovery (p < 0.01), whereas glucocorticoid-treated animals had lower endothelin-1 levels (4.5 +/- 2.1 pg/ml, preoperative and intraoperative glucocorticoids; 4.9 +/- 1.7 pg/mL, intraoperative glucocorticoids) at the end of recovery (p < 0.05). Intracellular adhesion molecule-1 in lung tissue was lower in animals receiving pre and intraoperative glucocorticoids (p < 0.05). Myeloperoxidase activity was elevated in control lungs at 2 hours of recovery compared with glucocorticoid-treated groups (p < 0.05). Inhibitor kappaBalpha, the inhibitor of nuclear factor-kappaB, was higher in lungs of animals receiving glucocorticoids compared with controls (p < 0.05). CONCLUSIONS: Glucocorticoids prevented pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest, which was associated with reduced plasma endothelin-1. Glucocorticoids also reduced pulmonary intercellular adhesion molecule-1 and myeloperoxidase activity. Inhibition of nuclear factor-kappaB, along with reduced neutrophil activation, contributed to glucocorticoid alleviation of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest.     

Sildenafil citrate alleviates pulmonary hypertension after hypoxia and reoxygenation with cardiopulmonary bypass

BACKGROUND: Sudden reoxygenation of hypoxic neonates undergoing cardiac operation exacerbates the systemic inflammatory response to cardiopulmonary bypass secondary to reoxygenation injury, worsening cardiopulmonary dysfunction. Reports suggest sildenafil decreases pulmonary hypertension and may affect myocardial function. Sildenafil's efficacy for treating postbypass cardiopulmonary dysfunction remains unknown. STUDY DESIGN: Fourteen neonatal piglets (5 to 7 kg) underwent 90 minutes of hypoxia, 60 minutes of reoxygenation with cardiopulmonary bypass, and 120 minutes of recovery. Six animals received 50 mg oral sildenafil and eight received saline at hypoxia. Data are presented as mean +/- SD. RESULTS: Sildenafil prevented the high pulmonary vascular resistance observed in controls (controls baseline 81 +/- 37 dynes. s/cm(5) versus recovery 230 +/- 93 dynes. s/cm(5), p = 0.004; sildenafil baseline 38 +/- 17 dynes. s/cm(5) versus recovery 101 +/- 60 dynes. s/cm(5), p = 0.003). Despite lower pulmonary vascular resistance after sildenafil, arterial endothelin-1 (ET-1) was increased in both groups (control baseline 1.3 +/- 0.5 pg/mL versus recovery 4.5 +/- 3.7 pg/mL, p = 0.01; sildenafil baseline 1.3 +/- 0.3 pg/mL versus recovery 9.8 +/- 4.9 pg/mL, p = 0.003). Intravenous nitric oxide (NO) levels were preserved after sildenafil treatment (sildenafil baseline 340 +/- 77 nM versus recovery 394 +/- 85 nM). IV NO levels in controls were decreased when compared with baseline (control baseline 364 +/- 83 nM versus recovery 257 +/- 97 nM, p = 0.028). Although levels of exhaled NO decreased in both groups, the sildenafil-treated animals had higher levels of exhaled NO when compared with controls at the end of recovery (0.6 +/- 0.4 parts per billion versus 1.8 +/- 0.9 parts per billion, respectively, p = 0.029). CONCLUSIONS: Sildenafil alleviated pulmonary hypertension after reoxygenation with cardiopulmonary bypass. Despite increased ET-1 levels, pulmonary vascular resistance was lower with sildenafil treatment, suggesting sildenafil's effect on the pulmonary vasculature is capable of countering vasoconstriction by ET-1. Further study into the role of sildenafil in perioperative therapy and its interactions with ET-1 are warranted.     

Recipients of blood from a donor with multiple HLA antibodies: a lookback study of transfusion-related acute lung injury

BACKGROUND: The effects of transfusion of HLA antibodies to patients with corresponding antigens are not well known. STUDY DESIGN AND METHODS: Records of patients who received blood from previous donations of a donor implicated in a case of transfusion-related acute lung injury (TRALI) were examined. The donor had multiple HLA antibodies reactive with 96 percent of HLA Class I antigens and 88 percent of HLA Class II antigens. RESULTS: Among 103 patients (40 with a pretransfusion white blood cell [WBC] count of >/=3.5 x 10(9)/L), 1 patient met criteria for TRALI and had clinical evidence for diffuse alveolar hemorrhage. Among the subset of 55 patients (17 with a pretransfusion WBC count of 3.5 x 10(9)/L) with known HLA types, none developed TRALI even though 54 (98%) had one to five corresponding HLA antigens. In a subgroup of patients four of 62 patients with chest radiographs, developed new or worse bilateral infiltrates with implicated but not control units (p = 0.0625). CONCLUSION: Transfusion of HLA antibodies from this donor to nonneutropenic patients did not cause TRALI, but there was a trend of an association with new or worse bilateral pulmonary infiltrates. Further research is needed to determine why transfusion of HLA antibodies to recipients with corresponding antigens causes TRALI in some cases and not in others.     

Treatment of Nevus comedonicus with topical tazarotene and calcipotriene

Nevus comedonicus is a rare developmental defect of the pilosebaceous unit. It is also thought to be a variant of epidermal nevus. Previously reported treatments include surgical excision, CO2 laser, dermabrasion, extraction, topical retinoic acid, and numerous topical keratolytics. We present a case of a 7-year-old boy with bilateral nevus comedonicus who experienced cosmetic improvement with topical tazarotene and calcipotriene cream. This combination represents a novel therapeutic approach to the treatment of this cutaneous abnormality.     

Clinical aspects of the disorders of GABA metabolism in children

PURPOSE OF REVIEW: There has been increased recognition of the pediatric neurotransmitter disorders. This review focuses on the clinical disorders of GABA metabolism. RECENT FINDINGS: The known clinical disorders of GABA metabolism are pyridoxine dependent epilepsy, GABA-transaminase deficiency, SSADH deficiency, and homocarnosinosis. Pyridoxine dependent epilepsy is diagnosed clinically but potentially more common presentations, with later and atypical features, widen the spectrum. No gene locus has been confirmed; the pathophysiology may involve alterations in PLP transport, binding to GAD, or other PLP-dependent pathways. SSADH deficiency is associated with developmental delay, prominent language deficits, hypotonia, ataxia, hyporeflexia, and seizures. Increased detection is reported when specific ion monitoring is used for GHB on urine organic acids. The most consistent MRI abnormality is increased signal in the globus pallidus. MR spectroscopy has demonstrated the first example of increased endogenous GABA in human brain parenchyma in this disorder. GABA-transaminase deficiency and homocarnosinosis appear to be very rare but require CSF for detection, thus allowing for the possibility that these entities, as in the other pediatric neurotransmitter disorders, are underrecognized. SUMMARY: The disorders of GABA metabolism require an increased index of clinical suspicion. Pyridoxine dependent epilepsy is a treatable condition with a potentially widening clinical spectrum, but with a prognosis dependent on early intervention. SSADH deficiency has a heterogeneous spectrum and requires careful urine organic acid testing for screening, followed by enzymatic confirmation allowing appropriate prognostic and genetic counseling.     

Evaluation of irofulven (MGI-114) in the treatment of recurrent or persistent endometrial carcinoma: A phase II study of the Gynecologic Oncology Group

OBJECTIVE: This multi-center phase II trial was conducted by the Gynecologic Oncology Group to evaluate the activity and toxicity of irofulven in patients with previously treated adenocarcinoma of the endometrium. METHODS: Eligible patients had documented recurrent or persistent endometrial carcinoma after receiving definitive locoregional therapy, and were required to have measurable disease, performance status of 0-2, and adequate bone marrow, hepatic and renal functions prior to study entry. Patients were allowed one prior chemotherapy regimen. The initial dose of irofulven was 11 mg/m(2)/day for four days administered intravenously. Cycles were repeated every 28 days. Doses were escalated or reduced based on previous cycle toxicity. RESULTS: Twenty-five patients were enrolled onto the trial. There was one (4%) confirmed complete response. Seven (28%) patients had stable disease, with a median duration of 10.4 (range: 4.4-21.6) months. Patients received a median of one (range: 1-5) cycle of protocol treatment. There were three early treatment-related deaths due to renal failure and severe electrolyte disturbances. Two patients experienced grade 4 hematologic adverse effects. CONCLUSION: Irofulven administered at the dose and schedule used in this trial was minimally active and resulted in significant toxicity.     

Children's ability to access and use health care

Under new regulations for Medicaid and the State Children's Health Insurance Program (SCHIP), states can extend health insurance to child enrollees' uninsured parents. We compared the extent to which child-only and family coverage (child and parent insured) ensure health care access and use for children in working-poor families. Among these children, 21 percent were uninsured, as were 30 percent of their parents. Children with no family coverage encountered more access barriers than insured children. Extending insurance to children markedly increases access and use. The additional benefits of family coverage over child-only coverage seem less pronounced, but family coverage expansions may narrow disparities in access.