Clinical methemoglobinemia secondary to administration of hydroxyurea at therapeutic doses in a dog.

Methemoglobinemia secondary to administration of hydroxyurea is only reported in veterinary medicine as a result of accidental ingestion of high doses, and once at therapeutic dose in human medicine. A 2.5-year-old female spayed mixed breed dog was presented for acute signs of neurologic disease and diagnosed with severe erythrocytosis without an identified underlying cause, leading to suspicion of polycythemia vera. The dog was managed with phlebotomies, supportive care, and administration of hydroxyurea. Within 2 h of administration of hydroxyurea (37 mg/kg) administration, respiratory distress with cyanosis, and methemoglobinemia developed. Signs resolved within 24 h but recurred after a second administration of lower dosage of hydroxyurea (17 mg/kg) 20 days later. The dog remained asymptomatic except for mild cyanosis but was humanely euthanized for lack of relevant improvement of signs of neurologic disease. This case report documents the repeated occurrence of methemoglobinemia in a dog after administration of hydroxyurea at therapeutic doses.

Clinical Presentation and Therapy of Ventricular Septal Defect.

Ventricular septal defects (VSDs) occur in 1.5-3.5 of 1000 live births and constitutes 20 % of congenital cardiac defects. There is no gender predominance.

Clinical Presentation and Therapy of Total Anomalous Pulmonary Venous Return.

Total anomalous pulmonary venous return (TAPVR) is rare (accounting for about 1% of all CHD) and can occur as a single lesion or in combination with other types of CHD (such as heterotaxy or HLHS). TAPVR is defined as an abnormal connection where all pulmonary veins do not drain into the left atrium but into the right atrium either directly or through a vein that is connected to the right atrium. TAPVR can be divided into four anatomic groups (Fig. 32.1): (1) supracardiac (about 55%), (2) cardiac (about 30%), (3) infracardiac (about 13%), and (4) mixed (very rare). In addition, it can be divided into two physiological types: nonobstructed and obstructed. Embryologically, all pulmonary veins usually connect to a pulmonary venous confluence that connects to the left atrium. If this connection does not occur, the pulmonary venous confluence connects to a systemic vein instead.

A Case Report of an Uncommon Association of Total Intracardiac Anomalous Pulmonary Venous Return and Tetralogy of Fallot.

Total anomalous pulmonary venous return (TAPVR) represents a group of anomalies consisting of a lack of connection between the pulmonary veins and the left atrium. All oxygenated pulmonary venous return flows directly or indirectly into the right atrium. Survival is only possible with a right-to-left atrial shunt. It remains rare, accounting for less than 1% of all congenital heart diseases. Its association with tetralogy of Fallot is much rarer and has been documented in medical literature as isolated cases. Early prenatal diagnosis, rapid surgical repair, and optimal postoperative resuscitation appear to be the best guarantee of a favorable outcome following total repair of a pulmonary venous connection anomaly. Non-obstructed forms present as high-flow shunts with moderate cyanosis. The symptomatology of blocked forms is dominated by the obstruction to venous return; a clinical picture of respiratory distress with intense cyanosis and severe pulmonary arterial hypertension develops from the first days of life. Echocardiography is fundamental in diagnosing TAPVR. If the results are inconclusive, magnetic resonance imaging and computed tomography are appropriate alternatives for establishing a complete and accurate diagnosis. We report a case of a two-month and 22-day-old infant who is a product of a twin pregnancy, presenting with a non-obstructed TAPVR associated with tetralogy of Fallot, and his twin who died on day 20 of life, likely due to a complex cyanotic congenital heart disease.

Beyond the Rib Cage: Unraveling Abernethy Syndrome as a Rare Cause of Cyanosis.

Abernethy syndrome is a rare congenital malformation stemming from a portosystemic shunt. Diagnosis proves challenging due to nonspecific clinical symptoms, with presentation varying based on age and disease severity. Consequences include hepatic, cardiovascular, renal, gastrointestinal, and neurological complications, and growth retardation. We report the case of a child presenting with perioral and digital cyanosis, observed in early childhood. Clinical examination revealed low saturation, telangiectasias, digital clubbing, and collateral venous circulation in the thorax. Imaging confirmed the diagnosis of Abernethy syndrome.

Methemoglobinemia Following Indoxacarb Ingestion: A Unique Toxicological Presentation.

Indoxacarb, an oxadiazine insecticide, is known for its selective lethality by blocking neuronal voltage-dependent sodium channels. While primarily developed to target insect populations resistant to other pesticides, its toxicity in humans remains poorly understood. We present a case of methemoglobinemia resulting from indoxacarb ingestion, a rare manifestation of its toxic effects. A 38-year-old farmer attempted suicide by ingesting the insecticide, leading to cyanosis, hypoxemia, and characteristic arterial blood gas findings indicative of methemoglobinemia. Prompt diagnosis was challenging due to the absence of specific tests, necessitating clinical suspicion. Treatment with methylene blue and supportive therapy resulted in significant clinical improvement, highlighting the importance of early intervention in managing indoxacarb poisoning. This case underscores the need for increased awareness among healthcare providers regarding the potential toxic effects of indoxacarb. It emphasizes the importance of prompt recognition and treatment of methemoglobinemia in pesticide-related poisonings. Further research is warranted to elucidate the mechanisms underlying indoxacarb toxicity in humans and to optimize treatment strategies for affected individuals.

Shades of Blue: A Case Series of Acquired Methemoglobinemia.

Acquired methemoglobinemia (MetHb) is a rare but potentially life-threatening condition that has varied etiology, usually toxin- or drug-induced. We had five cases of acquired methemoglobinemia during six months. Their presentation varied from an asymptomatic state to respiratory distress. The presence of cyanosis and low oxygen saturation (SpO2), despite normal partial pressure of oxygen (PaO2) and chocolate brown-colored blood, were diagnostic clues present in all cases. A high level of methemoglobinemia was detected on arterial blood gas (ABG), confirming the diagnosis. Methylene blue was used as an antidote along with supportive care in symptomatic cases. All these cases of methemoglobinemia recovered completely. A high index of suspicion for methemoglobinemia should be maintained in cases presenting with persistent hypoxia or cyanosis despite normal PaO2.

Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery.

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 µg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 µg/L/h, n = 58) (mean difference, 13.2 µg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

Rare type of tracheal agenesis: Unexpected presentation and immediate consideration of emergent esophageal intubation in neonatal resuscitation program. Case reports and review of the literature.

BACKGROUND: Tracheal agenesis, or tracheal atresia, is a rare congenital anomaly. The presence of a tracheoesophageal fistula (TEF) can help with breathing for newborns with tracheal agenesis. In this article, we presented three unique cases and outcomes of neonates with tracheal agenesis along with a review of the literature. METHODS: This study consisted of a single center case series followed by a review of literature. Case reports were generated using both written and electronic medical records from a single hospital. We summarized three unique cases and outcomes of neonates with tracheal agenesis and performed a review of the literature. RESULTS: We identified three cases of tracheal agenesis presented with severe cyanosis without spontaneous crying upon birth. Experienced pediatricians attempted to intubate the babies but were unsuccessful. Endotracheal tubes were subsequently either accidentally or purposely placed into the esophagus, and oxygen saturation levels improved. This suggested tracheal agenesis with TEF. Two cases underwent surgical intervention after resuscitation with esophageal intubation. CONCLUSION: Esophageal intubation may be a life-sustaining ventilation support for patients with tracheal agenesis and TEF at initial resuscitation. Clinicians should suspect tracheal agenesis when a newborn presents with severe cyanosis and voiceless crying upon birth, and esophageal intubation should be immediately attempted.

The Prevalence of Scoliosis after Fontan Circulation Surgery Followed-Up to Adolescence.

Introduction: The advancement of surgical techniques and perioperative management for congenital heart disease (CHD) has increased life expectancy. The surgical creation of the Fontan circulation maintains pulmonary blood flow without relying on an effective pump from the abnormal heart, relying on peripheral vascular resistance to maintain effective flow through the lungs. Unfortunately, this delicate mechanism is compromised when scoliosis restricts ventilation, leading to Fontan failure and a poor prognosis for life. This report describes the prevalence of scoliosis with Fontan completion surgery and the role of screening and surgical correction. Methods: Ninety-six consecutive Japanese patients undergoing Fontan completion surgery for CHD between 2000 and 2017 were identified in our institutional records. The inclusion criterion was at least 7 years of follow-up after Fontan completion surgery, while the exclusion criteria were congenital, syndromic, and neuromuscular scoliosis. Radiographic and clinical parameters, including cardio-thoracic ratio (CTR) for cardiomegaly and cyanosis saturation, were compared between with and without scoliosis. Results: There were 23 and 40 patients in the scoliosis and no scoliosis groups, respectively. The mean age at the final follow-up was 18.5 and 16.7 years in the scoliosis and no scoliosis groups, respectively (p=0.02). Mean CTR was 43.7% and 39.4% in the scoliosis and no scoliosis groups (p=0.016), and the mean saturation in room air at the final follow-up was 88.8% and 93.2%, respectively (p=0.036). There were no significant differences to clarify the risk factors with multivariate logistic regression analysis. Conclusions: The prevalence of scoliosis with Fontan completion surgery was 36.5%. Screening for scoliosis is important for children with Fontan circulation surgery as part of their routine follow-up at least until they reach adolescence.Evidence Level: 4.

A rare case of methemoglobinemia in a preterm newborn with unclear etiology.

 Cyanosis is a bluish discoloration of the tissues due to increased levels of deoxygenated hemoglobin in capillaries. It is a common finding in newborn infants that can be caused by different diseases, including pulmonary, cardiac, infectious, and hematological disorders. Methemoglobinemia is a rare cause of cyanosis, in which hemoglobin is oxidized, changing its heme iron configuration from the ferrous (Fe2 +) to the ferric (Fe3 +) state, creating methemoglobin (Met-Hb), a form that does not bind oxygen, leading to decreased oxygen delivery to the tissues and cyanosis. We report a rare case of a preterm newborn, who developed cyanosis and worsening hypoxemia on day ten of life, she was found to have elevated Met-Hb percentage in blood gas analysis that required treatment with intravenous methylene blue. Her symptoms resolved after a period of maintenance treatment with oral methylene blue and ascorbic acid, and the etiology of her disease remains unclear.

Impact of Age-Related Change in Caval Flow Ratio on Hepatic Flow Distribution in the Fontan Circulation.

BACKGROUND: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac conduit or a lateral tunnel connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. The effect of age-related changes in caval inflows on HFD was evaluated using cardiac magnetic resonance data and patient-specific computational fluid dynamics modeling. METHODS: SVC and IVC flow from 414 patients with Fontan were collected to establish a relationship between SVC:IVC flow ratio and age. Computational fluid dynamics modeling was performed in 60 (30 extracardiac and 30 lateral tunnel) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. RESULTS: SVC:IVC flow ratio inverted at ≈8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC, 2, 1, and 0.5 corresponded to ages, 3, 8, and 15+, respectively) was not significant for extracardiac but statistically significant for lateral tunnel cohorts. For all 3 caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2 to 0.5 (age, 3-15+) years, the correlation's strength decreased from 0.87 to 0.64, due to potential flow perturbation as IVC flow momentum increased. CONCLUSIONS: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of SVC:IVC variations over time on Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes.

A review of the current policies and guidance regarding Apgar scoring and the detection of jaundice and cyanosis concerning Black, Asian and ethnic minority neonates.

BACKGROUND: Ethnic inequalities in maternal and neonatal health in the UK are well documented. Concerns exist regarding the use of skin colour in neonatal assessments. Healthcare professionals should be trained to recognise symptoms of diverse skin tones, and comprehensive, and inclusive guidance is necessary for the safe assessment of all infants. Disparities in healthcare provision have been emphasised during the COVID-19 pandemic, and additional research is needed to determine whether such policies adequately address ethnic minority neonates. METHODS: A desktop search included searches of guidance produced for the United Kingdom (UK). Further searches of the Cochrane and World Health Organization (WHO) were used to identify any international guidance applicable in the UK context. RESULTS: Several policies and one training resource used descriptors 'pink,' 'pale,' 'pallor,' and 'blue' about neonatal skin and mucous membrane colour. No policies provided specific guidance on how these colour descriptors may appear in neonates with different skin pigmentation. Only the NICE guidance and HEE e-learning resource acknowledged the challenges of assessing jaundice in infants with diverse skin tones, while another guideline noted differences in the accuracy of bilirubin measurements for the assessment of jaundice. Three policies and one training resource advised against relying on visual observation of skin colour when diagnosing neonatal conditions. The training resource included images of ethnic minority neonates, although most images included white infants. CONCLUSIONS: Inadequate consideration of ethnicity in UK policy and training perpetuates disparities, leading to inaccurate assessments. A review is needed for inclusivity in neonatal care, regardless of skin pigmentation.

Causes of acquired methemoglobinemia - A retrospective study at a large academic hospital.

Methemoglobinemia is a potentially life-threatening condition caused by the formation of methemoglobin, a form of hemoglobin that cannot bind oxygen. While there are some rare congenital causes of methemoglobinemia, most cases are acquired from the effects of specific drugs or environmental exposures. In this retrospective study, we analyzed a large data set of whole blood samples analyzed for methemoglobin at an academic medical center in Midwestern United States that provides both pediatric and adult services. For a 14 year timeframe (May 2009- June 2023), we performed detailed chart analysis of all patients with a methemoglobin concentration of 3.1 % or higher. For an earlier 13 year timeframe (January 1996-April 2009), we performed chart review for all patients with a methemoglobin concentration of 10.0 % or higher. For the 2009-2023 data, dapsone was the most frequent cause of methemoglobinemia (methemoglobin 3.1 % or higher) in both pediatric (73.3 %, 115 clinical encounters, 105 unique patients) and adult (65.3 %, 195 clinical encounters, 190 unique patients) populations. Inhaled nitric oxide as medical therapy was the next most frequent cause in both pediatric (18.1 %) and adult (13.2 %) populations. Causes associated with two or more unique episodes with methemoglobin concentrations of 10.0 % and higher included the following: dapsone (n = 40 episodes), benzocaine (n = 10), recreational use of amyl or isobutyl nitrite (n = 3), suicide attempt with sodium nitrite (n = 3 with 1 fatality; all 3 cases within last 3 years), food contaminated with nitrates (n = 2), and sepsis (n = 2). A total of 18 patients received treatment with methylene blue including 5 cases associated with benzocaine and all of the cases associated with amyl nitrite, isobutyl nitrite, sodium nitrite, and contaminated food. Only 3 patients with dapsone-associated methemoglobinemia received methylene blue, reflecting primary management by dose reduction or discontinuation of drug. Overall, our data reinforce previous studies showing dapsone, inhaled nitric oxide, and nitrites as common agents causing methemoglobinemia in a patient population seen at a medical center. Our data also are consistent with recent epidemiology trends showing increase in suicide attempts using sodium nitrite.

Failing with Cyanosis-Heart Failure in End-Stage Unrepaired or Partially Palliated Congenital Heart Disease.

Heart failure in cyanotic congenital heart disease (CHD) is diagnosed clinically rather than relying solely on ventricular function assessments. Patients with cyanosis often present with clinical features indicative of heart failure. Although myocardial injury and dysfunction likely contribute to cyanotic CHD, the primary concern is the reduced delivery of oxygen to tissues. Symptoms such as fatigue, lassitude, dyspnea, headaches, myalgias, and a cold sensation underscore inadequate tissue oxygen delivery, forming the basis for defining heart failure in cyanotic CHD. Thus, it is pertinent to delve into the components of oxygen delivery in this context.

Early and Long-Term Clinical Outcomes of Ductal Stenting Versus Surgical Aortopulmonary Shunt Among Young Infants with Duct-Dependent Pulmonary Circulation.

Surgical aortopulmonary shunting (SAPS) and ductal stenting (DS) are the main palliations in infants with cyanotic congenital heart diseases (CHD). We aimed to study the safety and efficacy of DS and to compare it with SAPS as a palliative procedure in infants with CHD and duct-dependent pulmonary circulation. Retrospective institutional clinical data review of consecutive infants aged < 3 months who underwent DS or SAPS over 5 years. The primary outcome was procedural success which was defined as event-free survival (mortality, need for re-intervention, procedural failure) at 30 days post-procedure. The secondary outcome was defined by a composite of death, major adverse cardiovascular events, or need for re-intervention at 6 months and on long-term follow-up. We included 102 infants (DS, n = 53 and SAPS, n = 49). The median age at DS and SAPS was 4 days (IQR 2.0-8.5) and 8 days (IQR 4.0-39.0), respectively. The median weight at intervention was 3.0 kg (IQR 3.0-3.0) and 3.0 kg (IQR 2.5-3.0) in the two respective arms. Tetralogy of Fallot with pulmonary atresia was the most common indication for DS and SAPS. The 30-day mortality was significantly higher in SAPS group as compared with DS group (p < 0.05). However, 30-day major adverse cardiac events (MACE) rates were similar in both groups (p = 0.29). DS was associated with shorter duration of mechanical ventilation, duration of stay in the intensive care and hospital stay than with SAPS. At 6 months, there was no significant difference in terms of mortality or event-free survival. Long-term MACE-free survival was also comparable (p = 0.13). DS is an effective and safer alternative to SAPS in infants with duct-dependent pulmonary circulation, offering reduced procedure-related mortality and morbidity than SAPS. Careful study of ductal anatomy is crucial to procedural success. However, long-term outcomes are similar in both procedures.

Familial Psychomotor Delay of an Uncommon Cause: Type II Congenital Methemoglobinemia.

Methemoglobinemia is due to oxidization of divalent ferro-iron of hemoglobin to ferri-iron of methemoglobin (MetHb) which is incapable of transferring oxygen to tissues. This disease may be acquired by intoxication with oxidizing agents or inherited with a mutation of CYB5R3, the gene coding for the methemoglobin reductase or cytochrome B5 reductase 3 responsible for the reduction of MetHb to hemoglobin. We report the case of 2 sisters aged respectively of 15 and 8 months. They were born to a second-degree consanguineous marriage with a history of precocious and unexplained deaths in 3 relatives. Both sisters presented neurological features including psychomotor retardation, microcephaly, and axial hypotonia. Cerebral magnetic resonance imaging revealed cerebral atrophy in both cases associated with hypoplasia of the corpus callosum in the younger child. The association of neurological disability, cyanosis, and hypoxemia prompted a search for methemoglobinemia, with MetHB levels respectively of 26% and 15.8%in the 2 sisters. Initial treatment was based on methylene blue, then ascorbic acid. The genetic study revealed a c.463+8G>C mutation of CYB5R3 confirming the diagnosis of methemoglobinemia type II. The diagnosis of methemoglobinemia, although rare, should be considered in the presence of psychomotor retardation with cyanosis and subacute onset hypoxemia, especially in the presence of a family history.