Vasoactive Drugs in Pediatric Shock: In Search of a Paradigm.

To the Editor: It is with great interest that we read the article by Ramaswamy et al (1), published in a recent issue of Pediatric Critical Care Medicine, comparing the use of dopamine and epinephrine as a first-line drug for pediatric refractory hypotensive septic shock. As described in the study protocol, shock should be recognized in the first 5 minutes in order to initiate the primary therapeutic measures and fluid resuscitation. At the same time, parents were asked to sign the informed consent form. Parental comprehension and decision making in emergency scenarios are challenging. Did that process delay therapeutics during the study? Remarkably, only one patient refused consent, which is far below literature reports (2). What was the team approach that was used with families to achieve that result? A similar study by Ventura et al (3) compared dopamine and epinephrine in different doses (dopamine ranging from 5 to 10 μg/kg/min instead of 5–20 μg/kg/min) and reported an increased risk of death when administering dopamine compared with epinephrine. How did you calculate the bioequivalence between dopamine and epinephrine? Do you think that the higher dopamine doses, compared with the study of Ventura et al (3), were responsible for the lack of evidence of higher mortality in the patients who received dopamine? or was it simply a result of the small sample size? Another point of interest is the focus of infection, which are not matched. To compare sepsis resulting from a CNS focus (more prevalent in the dopamine group) to sepsis resulting from a pulmonary focus (more prevalent in the epinephrine We agree that there is a key question: Which are the goals we want to reach when we start treatment with acetazolamide? The majority of the authors use acetazolamide as a respiratory stimulant in mechanically ventilated patients to shorten the weaning period hampered by MA. However, acetazolamide’s efficacy in adult publications with chronic obstructive pulmonary disease patients remains still unclear (3, 4). In pediatric patients, the effect of acetazolamide on shortening the weaning period has not been assessed, and in addition, the decrease of Pco 2 after acetazolamide treatment in pediatric population has not been consistent throughout published studies. In our study, we found a decrease in Pco 2 in children who did not have underlying respiratory disease, but we did not collect data of the mechanical ventilation setting such as minute ventilation nor weaning parameters. Another possible goal to initiate a patient on acetazolamide could be to lower the bicarbonate and normalize the pH in MA situations to avoid a progressive worsening of MA that could facilitate a more beneficial condition when weaning is ready to begin. Furthermore, patients with increased serum bicarbonate levels have exhibited a higher morbimortality in ICU (5). Another interesting question is: From which magnitude of MA on can we consider treatment with acetazolamide? MA should be a steady and progressive state, with important physiologic derangements aside from slowing down weaning of mechanical ventilation. The removal of causative factors of MA should be taken into account before acetazolamide is initiated, as we commented in our work. Published studies have applied variable MA definitions to consider acetazolamide’s initiation (4, 6). We propose that PICU patients’ serum bicarbonate level should be at least over 30 mmol/L to start treatment with acetazolamide, although this value may be lower in patients who continue to be on high dose diuretic therapy. A third question that arises is: In which type of patients should treatment with acetazolamide be considered? We agree with Colombo and Codazzi (1) that acetazolamide may have a role in reducing hypoventilation in patients without respiratory disease. As we said, studies in adult populations include mainly chronic respiratory and often chronically hypercapnic patients with pure or mixed MA. In patients without underlying respiratory disease, but undergoing respiratory acute ill, persistent MA (posthypercapnic alkalosis) will be produced likewise, resulting of permissive hypercapnia utilization as protective lung strategy. An additional attention should be paid to the dead space to prevent inhalation of expired co 2 . Especially in younger patients with low tidal volumes, a proportionally higher dead space could lead to hypercapnia and MA, what could hinder an adequate response to acetazolamide treatment. Future studies should analyze acetazolamide’s efficacy in respiratory weaning in patients with and without respiratory pathology according to the results found in our study. The authors have disclosed that they do not have any potential conflicts of interest. Andrés José Alcaraz, PhD, Division of Pediatrics, Pediatric Getafe University Hospital, Getafe, Madrid, Spain, Universidad Europea de Madrid, Madrid, Spain; Maite Augusta Gil-Ruiz, MD, Division of Pediatric Critical Care, Gregorio Marañon General University Hospital, Madrid, Spain