Early exchange and pheresis therapies in critical pertussis*

This issue of Pediatric Critical Care Medicine includes a case report by Dr. Martinez and colleagues (1) on the use of exchange transfusion in a case of critical pertussis occurring in an 8-wk-old infant girl. To date, most reports of series of fatal Bordetella pertussis show a female prevalence in mortality (2, 3); although this may be confounded where immunization practices differ by gender. As well, the prevalence of pertussis critical illness in unimmunized, very young infants as compared with other age groups is well known (4, 5). Although the physiologic nature and etiology of these findings is beginning to emerge in ongoing studies as well as recent reports (6–8), it is encouraging to consider this report of the successful use of exchange transfusion to modify the course of this life-threatening and persistent problem. Critical pertussis illness is beginning to be described as “fulminant” and “malignant,” as differentiated from the outpatient coughing illness (9, 10). The prominent leukocytosis in this case (119,440 leukocytes per cubic millimeter) signified that organ failure and death were likely outcomes for this patient. Pulmonary hypertension (50 mm Hg calculated by tricuspid jet velocity) on the basis of occlusion of the pulmonary vascular tree via entrapment of abnormal leukocytes was severe. A recent report from France summarizes the pathophysiology of pulmonary arterial hypertension when pulmonary venous occlusion occurs in adults with diverse etiologies of the occlusive processes (11). Over time, diffuse intimal proliferation in the pulmonary vascular tree occurs, especially in the pulmonary venules and small veins. Such changes have presumably not taken place yet in the acute setting of critical pertussis with severe leukocytosis. We might expect that, in the acute setting, pulmonary veno-occlusive changes may be rapidly reversible in the young patient with critical pertussis illness, if the occluding white blood cells can be safely removed. The cyclic adenosine monophosphate overdrive induced by pertussis toxin exposure reported in laboratory models may mediate fundamental disruption in cell stress responses and immune signaling (12). This could explain the organ system failure described in postmortem series (13). Such disruption may be induced to a greater or lesser extent by the amount of pertussis toxin elaborated by a given strain of B. pertussis and at least partially explain the persistent of pertussis critical illness in infants even wherein immunization coverage rates are high (14). The imposition of cyclic adenosine monophosphate overdrive on a relatively anergic host may contribute to the pathology described in recent reports (9) that suggest lymphocyte depletion may be prominent in infants dying of B. pertussis infection. Evolution of B. pertussis in the postvaccine era in a manner that enables the fulminant course and organ failure seen in the pediatric intensive care unit (PICU) is one explanation currently being actively explored in the Eunice Kennedy Shrive National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (15, 16). This is a new model partnership between the Collaborative Pediatric Critical Care Research Network pediatric critical care investigators and an National Institute of General Medical Sciences-supported basic scientist seeking to understand the possibility of genomic variation, host microbe interaction, and strain ecology in B. pertussis critical illness pathogenesis (17). Treatment of pertussis critical illness remains challenging, even in the most tertiary of PICUs. Reports of the use of advanced transfusion practice in the PICU have included apheresis, plasmapheresis, and partial-, single-, and double-volume exchange transfusion. Such practices are not evaluated in large trials, nor in descriptive cohorts, and are described in anecdotal studies to have varying degrees of efficacy in ameliorating the life threatening processes that they are used to treat. In addition, the removal of leukocytes via exchange transfusion by using leukocyte depleted blood or with pheresis techniques is occasionally described (18, 19). One of the better-known uses for leukapheresis in the PICU is actually the severe leukocytosis that occurs at presentation (or relapse) of leukemia in the acute care setting. In adult acute myelogenous leukemia, hyperleukocytosis (defined in most reports as a white blood cell count of >100,000/mm3), leukapheresis is used to reduce the risks for the early mortality that arise from leukostasis in pulmonary and cerebral vessels. One recent retrospective report of a series of twenty-five such patients found definite reduction in early mortality risk and no procedural side effects or complications (20). Experience with exchange transfusion in critical pertussis, as in this issue's case report is not reported extensively, however. In pediatric critical illness, the use of exchange transfusion with leukodepleted blood, as well as the use of leukapheresis to treat the risks of leukostasis, are reported anecdotally (21, 22). This and many other critical care treatment strategies for critical pertussis illness await rigorous description, mechanistic understanding of therapeutic effect and risks, and hypothesis generation to inform studies of practices that are used in the PICU. An open and inquiring mind for the intensivist caring for a child with critical pertussis is the best way to move pediatric critical care medicine and treatment of critical pertussis forward. Carol E. Nicholson, MD National Institutes of Health, Bethesda, MD