Chronic granulomatous disease (CGD) is a primary immune deficiency due to defects in phagocyte respiratory burst leading to severe and life-threatening infections. Patients with CGD also suffer from disorders of inflammation and immune dysregulation including colitis and granulomatous lung disease, among others. Additionally, patients with CGD may be at increased risk of systemic inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH). The presentation of HLH often overlaps with symptoms of systemic inflammatory response syndrome (SIRS) or sepsis and therefore can be difficult to identify, especially in patients with a primary immune deficiency in which incidence of infection is increased. Thorough evaluation and empiric treatment for bacterial and fungal infections is necessary as HLH in CGD is almost always secondary to infection. Simultaneous treatment of infection with anti-microbials and inflammation with immunosuppression may be needed to blunt the hyperinflammatory response in secondary HLH. Herein, we present a series of X-linked CGD patients who developed HLH secondary to or with concurrent disseminated CGD-related infection. In two patients, CGD was a known diagnosis prior to development of HLH and in the other two CGD was diagnosed as part of the evaluation for HLH. Concurrent infection and HLH were fatal in three; one case was successfully treated, ultimately receiving hematopoietic stem cell transplantation. The current literature on presentation, diagnosis, and treatment of HLH in CGD is reviewed.
Objectives: Determination of neurologic death in children is a clinical diagnosis based on absence of neurologic function with irreversible coma and apnea. Apnea testing during determination of neurologic death assesses spontaneous respiration when Paco 2 increases to greater than or equal to 60 and greater than or equal to 20 mm Hg above pre-apneic baseline. The utility of transcutaneous carbon dioxide measurements during apnea testing in children is unknown. We seek to determine the degree of correlation between paired transcutaneous carbon dioxide and Paco 2 values during apnea testing for determination of neurologic death. Design: Single-center, retrospective case series. Setting: Twenty-eight bed PICU in a 259-bed, tertiary care, referral center. Patients: Children 0–18 years old undergoing determination of neurologic death between May 2017 and December 2018. Interventions: None. Measurements and Main Results: Primary outcomes were paired transcutaneous carbon dioxide and Paco 2 values obtained during determination of neurologic death. Primary analyses included Pearson correlation coefficient, Bland-Altman bias and limits of agreement, and comparative statistics. Descriptive data included demographics, admission diagnoses, hemodynamics, Vasoactive Inotropic Scores, and arterial blood gas measurement. Eight children underwent 15 determination of neurologic death examinations resulting in 31 paired transcutaneous carbon dioxide and Paco 2 values for study. Transcutaneous carbon dioxide and Paco 2 correlated well (r = 0.94; p < 0.01). Bias between transcutaneous carbon dioxide and Paco 2 was –3.29 ± 7.14 mm Hg. Differences in means did not correlate with Vasoactive Inotropic Score (r = 0.2) or patient temperature (r = 0.11). Receiver operator characteristic curve of transcutaneous carbon dioxide after 3–10 minutes of apnea to discriminate positive apnea testing by the standard of Paco 2 yielded an area under the curve of 0.91 and threshold of greater than or equal to 64 mm Hg (sensitivity, 91.7%; specificity, 100%; positive predictive value, 100%; negative predictive value, 92.3%; accuracy, 95.9%). Conclusions: During apnea testing for determination of neurologic death in children, noninvasive transcutaneous carbon dioxide monitoring demonstrated high correlation, accuracy, and minimal bias when compared with Paco 2. Further validation is required before any recommendation to replace Paco 2 with noninvasive transcutaneous carbon dioxide monitoring can be proposed. However, concurrent transcutaneous carbon dioxide data may limit unnecessary apnea time and associated hemodynamic instability or respiratory decompensation by approximating goal arterial blood sampling to document target Paco 2.
Discussion This study shows that a false increase in serum catecholamine induced by the administration of methyldopa level can be reduced by the simultaneous administration of barbiturate. Presumably methyldopa metabolism is accelerated by barbiturate. Buhs et al. (1964) showed that in man about half of ingested methyldopa is absorbed and that 50-90°0 of the amount absorbed is excreted within 48 hours. Of the metabolities methyldopa-mono-O-sulphate is found in largest quantities, and most probably the site of this phase of breakdown is the liver. Smaller amounts of 3-0-methyl-alphamethyldopa are demonstrable in the urine, and also alphamethyldopamine in the so-called neutral fraction, which is actually the first stage of methyldopa metabolism in man. Since at least part of methyldopa metabolism takes place in the liver and the effect of barbiturates on the microsomal enzymes of the liver has been proved, we suggest that methyl-dopa metabolism may be accelerated by barbiturates through enzyme induction. This phenomenon may have practical implications in the treatment of hypertensive patients. A West Indian child aged 13 months was found playing with white tablets and had one in his mouth. Fifteen minutes later he screamed loudly and became rigid. He remained rigid with intermittent crying until in the ambulance on the way to hospital, when he had a convulsion and a respiratory arrest. He was given mouth-to-mouth resuscitation and external cardiac massage. In the casualty department he continued to have fits repetitively and had five brief respiratory arrests within a short space of time. His airway was maintained and oxygen was given. During these convulsions he remained conscious and had facial grimacing with opisthotonos. At this time the nature of the tablets was unknown. Diazepam 2-5 mg given subcutaneously did not produce relaxation , but 2 5 mg intravenously, given in the course of an episode of severe muscle spasm complicated by respiratory arrest, produced immediate relaxation. His reflexes were still exaggerated and occasional extensor thrusts were evoked by minimal stimuli. By this time the tablets were morphologically identified as Easton's syrup (later confirmed by chromatography). Endotracheal intuba-tion was carried out after the intravenous administration of sux-amethonium and he was maintained with 100% oxygen and intermittent positive-pressure respiration. Gastric lavage was performed with sodium bicarbonate solution 45 minutes after ingestion of Easton's syrup tablets. An intramuscular injection of desferriox-amine mesylate was given because of the iron content of the tablets.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.