Acquired methemoglobinemia in children presenting to Italian pediatric emergency departments: a multicenter report.

INTRODUCTION: Methemoglobinemia (MetHb) is a rare inherited or acquired cause of cyanosis in children. Owing to its rarity, case reports and case series are mostly available in the current literature. This study reports data on a large sample of children with acquired MetHb. METHODS: Data on patients admitted for acquired MetHb between January 2007 to December 2020 was extracted from the databases of five Italian pediatric emergency departments (EDs). Demographical and clinical characteristics was reported and discussed. RESULTS: Nineteen cases of acquired MetHb were evaluated. Ten patients (52.6%) were male and 9 (47.4%) were female. The median age was 8.23 months. The median time from trigger to symptom onset was 6 hours. Mostly, the intoxication presumptively occurred by home ingestion of contaminated food, mainly badly preserved vegetable broth. All patients were cyanotic at admission, most patients also presented tachycardia and/or tachypnea, and two patients were comatose. Antidotal therapy with methylene blue was given in 14 patients (73.7%). The median hospital stay was 2 days. All patients survived. DISCUSSION: As MetHb leads to the pathognomonic brown blood discoloration, blood gas analysis is mandatory immediately upon hospital arrival of a cyanotic patient. A correct medical history is crucial to identify the trigger and remove it. In our sample, the age onset was much lower than in the previous literature, and MetHb mainly due to ingestion of contaminated vegetable broth. Methylene blue led to a rapid recovery in all patients. Oxygen therapy may well lead to complete recovery when methemoglobin levels do not exceed 30% in asymptomatic and 20% in mildly symptomatic patients. CONCLUSIONS: The diagnosis and management of acquired MetHb in the emergency setting requires acknowledgment of this condition as a cause of cyanosis in the weaning child. Indeed, when promptly recognized and treated, this severe condition rapidly resolves with no significant acute sequelae.

Gastrostomy Button Placement in Infants With Cyanotic Versus Acyanotic Congenital Heart Disease.

BACKGROUND: Infants with congenital heart disease (CHD) may exhibit increased metabolic demands, and many will undergo placement of a gastrostomy to achieve adequate nutritional intake. There is a paucity of data, however, comparing the operative risks and overall complications of gastrostomy placement in cyanotic versus acyanotic infants with CHD. We hypothesized that patients with cyanotic CHD would have a higher rate of gastrostomy-associated complications than infants with acyanotic CHD. METHODS: We retrospectively reviewed patients who underwent gastrostomy button placement after cardiac surgery for CHD between 2013 and 2018. Patients were stratified into cyanotic CHD and acyanotic CHD cohorts. Patient data were extracted from the Society of Thoracic Surgeons database and merged with clinical data related to gastrostomy placement and complications from chart review. Unadjusted analyses were used to find covariates associated with cyanotic CHD and acyanotic CHD, using a t-test or Wilcoxon rank-sum test for continuous data, depending on normalcy, and χ2 or Fisher's exact tests for categorical data depending on the distribution. RESULTS: There were 257 infants with CHD who underwent gastrostomy placement during the study period, of which 86 had cyanotic CHD. There were no significant differences in baseline weight or preoperative albumin levels between the two groups. Patients with cyanotic CHD had a lower incidence of comorbid syndromes (P = 0.0001), higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery scores (P < 0.0001), and higher postoperative mortality rate (P = 0.0189). There was a higher rate of granulation tissue formation in patients with acyanotic CHD (48.5% versus 22.1%, P < 0.0001). There were no differences in other gastrostomy button-related complications, including leakage, wound infection, or dislodgement. CONCLUSIONS: Patients with acyanotic CHD demonstrated a higher incidence of granulation tissue. We found no difference in gastrostomy-specific complication rates between the two groups, with the notable exception of granulation tissue formation. Based on this study, the diagnosis of cyanotic CHD does not increase the risk of gastrostomy-related complications.

Acute bilateral hand edema and vesiculation.

Environmental history exposed the diagnosis.

Guidelines for Thrombolytic Therapy for Frostbite.

The data are insufficient to support standardized treatment of all patients with frostbite with thrombolytic therapy. The following guidelines, however, should be applied to all patients with cyanosis persisting proximal to the distal phalanx (Grade 3 or 4 frostbite injury) and demonstrated loss of perfusion at or proximal to the middle phalanx immediately after rewarming.

Brief Resolved Unexplained Events: Analysis of an Apparent Life Threatening Event Database.

OBJECTIVE: To identify the proportion of patients previously diagnosed with apparent life-threatening events (ALTE) who would meet criteria for brief resolved unexplained events (BRUE) and to identify rates of adverse outcomes in subgroups: ALTE not meeting criteria for BRUE, lower-risk BRUE, and higher-risk ALTE. METHODS: We performed a secondary analysis of a single-center prospective registry of patients diagnosed with ALTE in a tertiary care emergency department from March 1, 1997 to October 31, 2007. We identified the proportion of patients meeting criteria for BRUE, and the proportion of patients with BRUE meeting lower-risk criteria. We assessed outcomes of patients in subgroups. RESULTS: Seven hundred and sixty-two patients were included. Adverse outcomes included recurrent ALTE (n = 49), aspiration (n = 9), trauma (n = 8), and death (n = 4). Three hundred and twenty-six of 762 (42.8%) met criteria for BRUE. Seventy of 326 (21.5%) met criteria for lower-risk BRUE. Adverse outcomes occurred in 40 of 436 (9.2%) with ALTE not meeting criteria for BRUE, 2 of 70 (2.9%) with lower-risk BRUE, and 23 of 256 (9.0%) with higher-risk BRUE. Of 4 patients who died, 1 had an ALTE not meeting criteria for BRUE and 3 had non-lower-risk BRUE. The BRUE risk criteria identified all BRUE patients that died or had substantial morbidity as higher-risk. CONCLUSIONS: Less than half of patients with ALTE meet criteria for BRUE. Of those who do, one-fifth is lower-risk. In this series, the risk-stratification in the BRUE criteria identified those patients at highest risk of adverse outcomes. Further research is required to risk-stratify patients with BRUE.

[Effect of sodium acetate Ringer injection on perioperative fluid therapy in children with cyanotic congenital heart disease].

OBJECTIVE: To evaluate the efficacy of volume therapy with sodium acetate Ringer solution during the perioperative period in children with cyanotic congenital heart disease (CHD). METHODS: The children who underwent elective surgery for cyanotic CHD admitted to Shanghai Children's Medical Center Affiliated to the Medical School of Shanghai Jiaotong University from September to December 2018 were divided into three groups according to random number table with the informed consent of their legal representatives. All of the children received volume therapy with infusion of sodium acetate Ringer solution intravenously upon anesthesia induction. The volume of infusion was calculated according to the "4-2-1" formula (group A, the rehydration volume was 4 mL×kg-1×h-1 for the first 10 kg body weight, 2 mL×kg-1×h-1 for the second 10 kg, and 1 mL×kg-1×h-1 for the third 10 kg and above), and the volume was increased by 50% or 100% in groups B and C, respectively. The intravenous infusion lasted for 30 minutes in all the three groups. Arterial blood gas analysis was performed before and 30 minutes after infusion to observe the acid-base status and electrolyte level. Pulse oxygen saturation (SpO2), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) before and 10, 20, 30 minutes after infusion, central venous pressure (CVP) at 30 minutes after infusion were recorded, as well as adverse events occurred after infusion. RESULTS: Twenty-six children with cyanotic CHD, 17 male and 9 female, aged from 1 to 36 months, body weight 3.6 to 16.0 kg, and America Society of Anesthesiologists (ASA) level of III or IV, were enrolled in the study. The pH value in group B at 30 minutes after infusion was significantly higher than that before infusion (7.35±0.05 vs. 7.32±0.06, P < 0.05), while no significant changes were found before and after infusion in the other two groups. The hematocrits (Hct) after infusion in three groups were significantly lower than those before infusion (0.433±0.141 vs. 0.473±0.146 in group A, 0.324±0.054 vs. 0.372±0.063 in group B, 0.363±0.097 vs. 0.418±0.111 in group C, all P < 0.01), indicating that all the children in the three groups achieved effective hemodilution. However, there was no significant difference in blood gas analysis before and after infusion among the three groups. The level of blood lactic acid (Lac) in all CHD children was decreased from (1.33±0.63) mmol/L to (0.98±0.36) mmol/L after infusion of sodium acetate Ringer solution, the serum Ca2+ concentration was decreased from (1.22±0.06) mmol/L to (1.19±0.06) mmol/L, and the serum Cl- concentration was increased from (108.74±2.70) mmol/L to (109.77±2.54) mmol/L with the statistically significant differences (all P < 0.01). However, no significant difference was found in Lac or electrolyte levels before and after infusion among the three groups. There was no significant difference in vital signs before and after infusion among the three groups, but the period of infusion had an effect on SpO2 (F = 5.998, P < 0.01), HR (F = 34.279, P < 0.01) and SBP (F = 4.345, P < 0.05). HR in groups A and C were significantly lower than those before infusion, and SBP in group A was decreased gradually with the prolongation of infusion time. The CVP value at 30 minutes after infusion in group B was higher than that in group A. No adverse reactions such as rash or anaphylactic shock occurred after infusion of sodium acetate Ringer solution in all children. CONCLUSIONS: The perioperative volume therapy with sodium acetate Ringer solution in children with cyanotic CHD can effectively prevent the increase in Lac level and does not aggravate metabolic acidosis. The volume of infusion was well tolerated by all the children without disturbing the hemodynamic parameters.

Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: the APPEAR randomized trial.

BACKGROUND: In newborns and small infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) and blood priming, it is unclear whether there is reduced blood loss if fresh frozen plasma (FFP) is added to the CPB priming volume. This single-centre, randomized trial tested the hypothesis that the administration of FFP after CPB (late FFP group) is superior to FFP priming (early FFP group) in terms of postoperative bleeding and overall red blood cell (RBC) transfusion. METHODS: Seventy-three infants weighing <10 kg were randomly allocated to receive FFP to supplement RBCs in the CPB priming solution ( n =36) or immediately after CPB ( n =37). The primary endpoint was a difference in postoperative blood loss; secondary endpoints included the amount of RBCs and FFP transfused through the first 48 postoperative hours. RESULTS: All patients were included in the analysis. Patients in the late FFP arm had greater postoperative mean blood loss than patients in the early FFP arm [33.1 ( sd 20.6) vs 24.1 (12.9) ml kg -1 ; P =0.028], but no differences in transfusions were found. The subgroup of cyanotic heart disease patients had comparable results, but with greater use of RBCs in the late FFP group. CONCLUSIONS: In infants undergoing cardiac surgery, FFP in the priming solution appears slightly superior to late administration in terms of postoperative bleeding. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov , NCT02738190.

Unexpected episodes of cyanosis in late preterm and term neonates prompted admission to a neonatal care unit.

BACKGROUND: We studied late preterm and term infants who were admitted to our neonatal care unit in a tertiary hospital for unexpected episodes of cyanosis that occurred during rooming-in for evaluation of their frequency, most frequent associated diseases, and documentation of the diagnostic clinical approach. METHODS: We carried out a retrospective study of infants with a gestational age ≥35 weeks who were admitted from the nursery with the diagnosis of cyanosis from January 2009 to December 2016. Exclusion criteria were the occurrence of acrocyanosis and the diagnosis of sudden unexpected postnatal collapse (SUPC). RESULTS: We studied 49 infants with a mean gestational age of 38 ± 2 weeks. The frequency of admission for cyanosis was 1.8/1000 live births and was similar (p = 0.167) in late preterm and term infants. The majority of episodes occurred during the first 24 h of life (57%). Only 16 infants (33%) were discharged with a diagnosis, that was mostly (n = 5;10%) gastro-esophageal reflux. CONCLUSIONS: Unexpected episodes of cyanosis caused admission of 1.8/1000 live births to the neonatal care unit without differences between late preterm and term infants. These episodes occurred mainly during the first day of life and infants were mostly discharged without a known diagnosis.

Brief resolved unexplained event: New diagnosis in infants.

QUESTION: For many years, the term apparent life-threatening event (ALTE) was associated with sudden infant death syndrome, and parents who described an acute event in their infants were sent to the hospital for admission. I understand that for infants new terminology is recommended. What is the current approach to a near-death experience of an infant? ANSWER: A recent clinical practice guideline revised the name and definition of an ALTE to a brief resolved unexplained event (BRUE). The diagnosis of BRUE in infants younger than 1 year of age is made when infants experience 1 of the following BRUE symptoms: a brief episode (ie, less than 1 minute and usually less than 20 to 30 seconds) that is entirely resolved (infant is at baseline), which remains unexplained after the history and physical examination are completed, and includes an event characterized by cyanosis or pallor; absent, decreased, or irregular breathing; hypertonia or hypotonia; or altered responsiveness. Low-risk infants should not be admitted to the hospital and overtesting is discouraged.

The effects of iron treatment on viscosity in children with cyanotic congenital heart disease.

OBJECTIVE: This study was planned to determine the effects of iron treatment in children with cyanotic congenital heart disease. METHOD AND MATERIALS: A total of 39 patients with cyanotic congenital heart disease including 20 (51%) females, 19 (49%) males and whose mean age was 9.9 ± 6.2 years, average weight was 33 ± 18.4 kg were evaluated. Patients were categorized into two groups as having iron deficiency and no iron deficiency with respect to their ferritin levels. 4 mg/kg/day iron treatment with two valences was applied to the groups with iron deficiency for 3 months. Clinical and laboratory findings of both groups were assessed at the outset and 3 months later and viscosity measurements were carried out. RESULTS: Iron deficiency was identified in 21 (53.8%) out of 39 patients. Average Hb and Hct values following 3-month iron treatment increased from 14.8 ± 2.4 g/dl to 16.0 ± 2.0 (P = 0.003) and from %45.8 ± 7.5 to %47.6 ± 7.2 (P = 0.052), respectively. Average viscosity value, however, was 5.6 ± 1.0 cP, it reduced to 5.5 ± 1.0 cP value by demonstrating very little reduction (P = 0.741). Nevertheless, O2 sat value increased from 71.7 to 75% and complaints such as headache, visual blurriness, having frequent sinusitis decreased. CONCLUSIONS: It was observed that iron treatment increased Hb and Hct levels in patients with cyanotic congenital heart disease without raising viscosity and it ensured improvement in clinical symptoms.

Evaluation of Adults With Congenital Heart Disease.

The clinical approach to adults with congenital heart diseases (ACHDs) is unique in cardiovascular medicine because these patients encompass a broad range of presentations. Each patient, despite having similar diagnosis, will be anatomically and physiologically unlike others within ACHD population, in relation to the type of repair, age at repair, associated defects, with specific long-term risk factors and complications. Furthermore, as many patients will not complain of symptoms, clinical evaluation and diagnostic testing must also be based on the underlying main diagnostic category, with complete standardized lesion-specific clinical protocols, investigating all known risk factors specific for each congenital heart disease and performed as part of screening for significant long-term complications. The first part of this review will focus on clinical history, physical examination, and the most important diagnostic testing in ACHD population. The second part of the article will focus on some clinical issues we have to face in our daily practice, such as heart failure, cyanosis, and pulmonary hypertension. Furthermore, as survival rates of ACHD population continue to improve and patients with this condition live longer, we will briefly report on a new clinical concern regarding the impact of acquired morbidities like coronary artery disease that appear to be of greater importance in defining outcome in older patients with ACHD.

An Uncommon Complication With Use of Topical Local Anesthetic Agents: Methemoglobinemia.

Although the use of topical local anesthetics is generally safe, several potentially fatal complications have been reported. Methemoglobinemia is a rare but potentially fatal complication. Methemoglobin is a naturally occurring oxidized metabolite of hemoglobin, and physiologic levels (<1%) are normal. Methemoglobinemia can be congenital or acquired. Several drugs including topical anesthetic agents like benzocaine can induce this condition. Sudden appearance of cyanosis, with a disproportionately better oxygen saturation of 85% after use of local anesthetics can be a helpful for diagnosis.

Sickle Cell Disease with Cyanotic Congenital Heart Disease: Long-Term Outcomes in 5 Children.

Sickle cell disease is a risk factor for cerebrovascular accidents in the pediatric population. This risk is compounded by hypoxemia. Cyanotic congenital heart disease can expose patients to prolonged hypoxemia. To our knowledge, the long-term outcome of patients who have combined sickle cell and cyanotic congenital heart disease has not been reported. We retrospectively reviewed patient records at our institution and identified 5 patients (3 girls and 2 boys) who had both conditions. Their outcomes were uniformly poor: 4 died (age range, 12 mo-17 yr); 3 had documented cerebrovascular accidents; and 3 developed ventricular dysfunction. The surviving patient had developmental delays. On the basis of this series, we suggest mitigating hypoxemia, and thus the risk of stroke, in patients who have sickle cell disease and cyanotic congenital heart disease. Potential therapies include chronic blood transfusions, hydroxyurea, earlier surgical correction to reduce the duration of hypoxemia, and heart or bone marrow transplantation.