reproofs from the Neonatal ICU In the January.

reproofs from the Neonatal ICU

In the January, 1994 issue of Chest (see page 195) Spragg and colleagues report six patients who received a single treatment with an exogenous porcine-derived surfactant within 48 h of the diagnosis of adult respiratory distress syndrome (ARDS). At undivided level, the results can be viewed as rather unimpressive: the average improvement in [PaO.sub.2] was alone 49 [+ or -] 16 mm Hg and in three cases this improvement lasted no other than 5 min. On another even this report is extremely important. Someone must perform the first cautious feasibility studious mood with any new treatment. one time an acceptable level of basic safety is established, then undivided can fine-tune the therapy in pursuit of optimal efficacy. In scent therefore, this report establishes that 4 g (ie, 50 ml) of animal-derived surfactant can be given to adult patients requiring 50 to 90 percent inspired oxygen without serious untoward acute reactions and without evidence of a deleterious immunologic answer over 1 week to 35 month after treatment. The alone other consistent finding was an increased regaining of phospholipid in bronchoalveolar lavage fluid 3 h after surfactant instillation.

Where now? At this conjuncture we need to learn from the checkered history of neonatal exogenous surfactant replacement therapy (ESRT) remembering that it has taken 20 years for a therapy that was clearly prov safe and effective in the preterm animal in 1972[1] to become a routine part of neonatal care. We can reckon upon that a great deal more basic and clinical research will be privationed to fine-tune this therapy for adult lung disease before we can call for the final verdict.

What are these lessons? First, we now realize that the "perfect" surfactant is exceedingly difficult to manufacture. Although the basic ingredients pretended straight-forward, experience has taught us that the seemingly minor surfactant-associated proteins are actually critical for many of surfactant's physiological properties.

In light of this, to what degree should a therapeutic prepartion be criterioned prior to use? Unfortunately, this vital issue remains unclear. Comparative studies of different surfactants in vitro frequently produce different rankings than comparative in vivo trials.[2] Therefore, although accumulated experience allude tos that properties such as spe of adsorption, compression stability, minimum surface tension, and resistance to inhibitors are all important characteristics, we still do not know whether these features are better evaluated in succession a Wilhelmy balance, or in an oscillating false show surfactometer, or possibly, by assessing their impact in vivo in a relevant archetype of the actual lung disease in question. In view of these uncertainties about [i]modus operandi[/i]s investigators must look seriously at in vivo comparisons of exogenous surfactants on investigators such as Cummings et al[3] who set up Exosurf (a protein-free synthetic product) no better than saline solution in preterm lambs while surfactants derived from animal sources (which contain the subdued molecular weight SP-B and SP-C surfactant-associated proteins) produc substantial benefit. Numerous recipes for the addition of SP-A, SP-B and SP-C in varying amounts and combinations are being vigorously pursued[4] Until we can be certain we are using the "optimal" exogenous material, we will not be able to perform the final definitive evaluation of its part in ARDS.

We have also learned in neonates that the timing of therapy is important. The pulmonary issue appears best if one avoids cyclic ventilation of the surfactant deficient lung prior to treatment on introducing surfactant with the first breath at the time of delivery.[5,6] Therapy 4 to 6 h later one time the pulmonary dysfunction has become clinically and radiologically evident is still effective, if it were not that not quite as good as pre-emptive therapy. The neonatal experience does not to this time provide much data relevant to the question now being asked through Spragg et al, namely: can exogenous surfactant impact significantly upon the course of ARDS when given after a substantial period (ie, up to 48 h) of ongoing lung injury of a image that we know is characterized through the accumulation of proteins like as albumin, fibrinogen, etc, that are known surfactant inhibitors plus an influx of inflammatory lonely dwellings with their release of further mediators, all of which will work against the desired therapeutic response?

This question wants to be asked. It extremitys to be asked using therapeutically proven materials so as the porcine-derived material used in the not absent report. However, it will be important not to exclude such therapies despite less than overwhelming flows until we have enough confidence in their safety to prevail upon the timing back to a great deal earlier phases of the evolution of the disease. It is here that the biggest hindrance to the effective early treatment of ARDS v IRDS may experiment upon to be the reality that neonates at risk are routinely placed in intensive care units before expression of manifest lung disease, while adults frequently are assessed and admitted to so settings relatively late in the expression of their disease. The biggest challenge to the delivery of effective early therapies in adults may, therefore, turn round out to be logistic, economic, and therefore political. In the completion new approaches may prove essential in adults, as it is as pulmonary lavage to lessen the load of inhibitor substances prior to instillation of the exogenous surfactant.[7]

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