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Objective: The authors hypothesized that TNF would induce eicosanoid synthesis, and a cyclooxygenase inhibitor would attenuate both eicosanoid synthesis and improve survival in an LD90 TNF-induced (150 ng/kg/i.v./5 min) mortality model., Summary Background Data: Tumor necrosis factor is a cardinal mediator in sepsis; however, little is known about its effects on arachidonate metabolism., Methods: Conscious male rats with carotid arterial and jugular venous catheters were randomized for mortality: group I, TNF alone (150 kg/i.v./15 min, n = 30); group II, ibuprofen (30 mg/kg/i.v. at t = -20 and +240 min), plus TNF, (n = 28); and for hemodynamics, eicosanoid synthesis, blood gases: group III, TNF alone, (n = 8); group IV, ibuprofen + TNF (n = 8); group V, monoclonal antibody to TNF plus TNF (n = 8). Mortality was determined at 4-72 hr. Other parameters determined over 4 hours (0, 5, 60, 120, 240 min)., Results: TNF stimulated synthesis of (a) TXB2 (71 +/- 30 pg/ml, mean +/- SE at base vs. 117 +/- 18 at 4 hr, p < 0.02); (b) PGE2 (70 +/- 6 pg/ml at base vs. 231 +/- 68 at 4 hr, p < 0.02); (c) 6PGF (52 +/- 6 pg/ml at base vs. 250 +/- 80 at 4 hr, p < 0.02). Ibuprofen significantly (p < 0.05) inhibited eicosanoid synthesis from TNF. TNF-induced mortality (87%, 26/30) was dramatically decreased with ibuprofen (11%, 3/28), at 4, 24, and 72 hr (p < 0.01). Monoclonal antibody to TNF prevented all abnormalities and had 100% survival. Hemodynamic events were similar in both groups, but metabolic acidosis was attenuated with ibuprofen., Conclusions: TNF stimulates arachidonic acid metabolism in vivo. A cyclooxygenase inhibitor attenuates eicosanoid synthesis and dramatically improves survival. TNF appears to have different effect on tissues that synthesize certain eicosanoids. Hypotension from TNF is not mediated via the eicosanoids. TNF-induced mortality, like endotoxemia/sepsis may be mediated, in part, via arachidonic acid metabolites. These new findings support the notion that cyclooxygenase inhibitors may be used as adjunctive therapy in clinical sepsis.

Respiratory failure is the leading cause of death in the newborn. Conventional therapy is very successful with 80% of infants weaned from ventilatory support. For neonates with severe respiratory failure, unresponsive to maximal medical therapy, extracorporeal membrane oxygenation (ECMO) offers an alternative means of management. Venoarterial bypass is achieved by cannulating the right atrium via the internal jugular vein and the aortic arch via the right common carotid artery. A 5-inch roller pump is used to circulate the blood through a 0.4 or 0.8 m2 silicone membrane lung. Management includes heparinization, intravenous alimentation, antibiotic coverage, and reduction of FiO2 and airway pressure. Thirty infants aged 12 to 186 hours were placed on ECMO. Each met strict criteria designed to predict greater than 90% mortality. Time on bypass ranged from 37 to 250 hours. Success, defined by weaning from ECMO and ventilatory support, was achieved in 23. Twenty-one remain alive; 18 have excellent outcome with normal growth and development although follow-up is short (1 to 19 mos). These results corroborate reports from the pioneers of the technique and further support the use of ECMO for neonates with respiratory failure unresponsive to conventional therapy.

Meconium aspiration syndrome (MAS) is a common cause of morbidity and mortality in neonates. Chemical pneumonitis can lead to persistent pulmonary hypertension of the newborn (PPHN) with irreversible hypoxia and death. Extracorporeal membrane oxygenation (ECMO) for the treatment of severe PPHN became available at the Ochsner Foundation Hospital in September 1983. We reviewed the first 28 cases in which ECMO was used for the treatment of PPHN due to severe MAS; 26 of the 28 infants survived. During the three years preceding our development of ECMO capability, ten neonates had PPHN due to severe MAS and met the criteria for ECMO; only three survived. The difference in survival demonstrates the efficacy of ECMO for the treatment of severe MAS. We believe that when established criteria are met, ECMO should be instituted without delay.

Respiratory failure is the leading cause of death in the neonatal period. The anatomic and functional basis for this, particularly in full-term infants, most often is persistent pulmonary hypertension of the neonate (PPHN). This condition is reversible but can cause very severe and unrelenting respiratory failure and ultimate death when uncontrolled. Recent technologic advances have expanded the scope of therapy available for PPHN, resulting in increasing therapeutic success for these critically ill infants. This article reviews the anatomic and functional anomalies of PPHN, as well as the methods of diagnosis and discusses current treatment.