Three Cases of Pediatric Multisystem Inflammatory Syndrome Associated with COVID-19 Due to SARS-CoV-2.

BACKGROUND Coronavirus disease 2019 (COVID-19) infection commonly presents as fever, cough, and shortness of breath in adults. Children are thought to have milder respiratory symptoms and to recover more quickly. We describe a new presentation of COVID-19 infection in children consisting of multisystem inflammation with decreased left ventricular function and evidence of lung disease. CASE REPORT Three children presented with fever, conjunctivitis, dry and cracked lips, rash, and/or cervical lymphadenopathy for at least 5 days. Two of these children required mechanical ventilation, and 1 of the 2 needed extracorporeal membrane oxygenation (ECMO) to support cardiorespiratory function. All of these children had moderate to severe hyponatremia and lymphopenia, which is usually seen in COVID-19. They were treated with intravenous immunoglobulin and high-dose aspirin. All of the children recovered. CONCLUSIONS Early recognition of children with multisystem inflammation is important because they are at increased risk for deterioration. Treatment with intravenous immunoglobulin and aspirin was used because this regimen has been shown to be beneficial in vasculitis of Kawasaki disease. The development of shock due to cardiac involvement may require ECMO.

High Frequency Jet Ventilation in Respiratory Failure Secondary to Respiratory Syncytial Virus Infection: A Case Series.

OBJECTIVE: To describe the utility of high frequency jet ventilation (HFJV) as a rescue therapy in patients with respiratory failure secondary to respiratory syncytial virus (RSV) that was refractory to conventional mechanical ventilation (CMV). DESIGN: Descriptive study by retrospective review. SETTING: Pediatric intensive care unit at a tertiary care children's hospital. PATIENTS: Infants on mechanical ventilation for respiratory failure due to RSV. INTERVENTIONS: Use of HFJV. MAIN RESULTS: Eleven patients were placed on HFJV. There was sustained improvement in ventilation on HFJV with a mean decrease in PCO2 of 9 mmHg at 24 h and 11 mmHg at 72 h. There were no significant changes in oxygenation by oxygenation index. No patients required extracorporeal support or suffered pneumothorax, pneumomediastinum, or subcutaneous emphysema. Ten out of 11 (91%) patients survived to discharge from the hospital. CONCLUSION: High frequency jet ventilation may represent an alternative therapy for RSV-induced respiratory failure that is refractory to CMV.

Views of pediatric intensive care physicians on the ethics of organ donation after cardiac death.

OBJECTIVE: Donation after cardiac death has been endorsed by professional organizations, including the American Academy of Pediatrics as a means of increasing the supply of transplantable organs. However, ethical concerns have been raised about donation after cardiac death, especially in children. This study explores the views of pediatric intensive care physicians on the ethics of pediatric donation after cardiac death. DESIGN: Internet survey. SUBJECTS: Physician members of the American Academy of Pediatrics Section of Critical Care. INTERVENTIONS: Physicians were emailed an anonymous survey consisting of four demographic items and 16 items designed to assess their views on the ethics of pediatric donation after cardiac death. Responses to ethics items were rated on a 5-point scale ranging from strongly disagree to strongly agree. Physicians were also given the opportunity to provide free-text comments regarding their views. MEASUREMENTS AND MAIN RESULTS: Of the 598 eligible physicians, 264 (44.1%) responded to the survey. Of these, 193 (73.4%) were practicing in a transplant center and 160 (60.6%) participated in at least one donation after cardiac death procedure at the time of survey completion. Two hundred twenty (83.4%) agreed or strongly agreed that regarding donation after cardiac death, parents should be able to make decisions based on the best interests of their child. Two hundred twenty-two (84.1%) agreed or strongly agreed that it is not acceptable to harvest organs from a child before the declaration of death, consistent with the Dead Donor Rule. However, only 155 (59.1%) agreed or strongly agreed that the time of death in donation after cardiac death can be conclusively determined. Twenty-nine (11.0%) agreed or strongly agreed that the pediatric donation after cardiac death donor may feel pain or suffering during the harvest procedure. CONCLUSIONS: Most pediatric intensive care physicians agree that the Dead Donor Rule should be applied for donation after cardiac death and that donation after cardiac death can be consistent with the best interest standard. However, concerns about the ability to determine time of death for the purpose of organ donation and the possibility of increasing donor pain and suffering exist.

Copeptin as a marker of relative arginine vasopressin deficiency after pediatric cardiac surgery.

PURPOSE: Relative arginine vasopressin (AVP) deficiency after pediatric cardiac surgery has recently been described. Copeptin, a more stable and easily measured product of pro-AVP processing, may be a means of identifying these patients. We aimed to determine if copeptin was correlated with AVP in these children and whether it can be a surrogate marker of relative AVP deficiency. METHODS: Patients <6 years of age with basic Aristotle scores ≥7 requiring surgery with cardiopulmonary bypass were prospectively enrolled. Plasma AVP and copeptin concentrations were measured pre-cardiopulmonary bypass and 4 and 24 h post-cardiopulmonary bypass. Relative AVP deficiency was defined a priori based on our previous work as AVP <9.2 pg/ml at 4 h post-cardiopulmonary bypass. RESULTS: Of 41 children enrolled, relative AVP deficiency was present in 13 (32 %). AVP and copeptin concentrations were significantly lower in these 13 children at 4 h post-cardiopulmonary bypass as compared to the other 28 patients. A significant positive association between plasma AVP and copeptin concentrations over time was determined. Based on log-transformed analyses, a 1 % increase in plasma AVP led to a 0.19 % increase in copeptin. Further, copeptin <1.12 ng/ml at 4 h post-cardiopulmonary bypass had a sensitivity of 92 % and a negative predictive value of 95 % for relative AVP deficiency. CONCLUSIONS: Plasma AVP and copeptin are positively associated in children undergoing cardiac surgery. Copeptin may represent a useful means of identifying relative AVP deficiency in these patients.

Mechanism of lactic acidosis in children with acute severe asthma.

OBJECTIVE: Hyperlactatemia and lactic acidosis are common in adults with acute severe asthma however only a few cases have been reported in children. Type A lactic acidosis is associated with impaired oxygen delivery; type B occurs in the presence of normal oxygen delivery and has been described to occur with excessive adrenergic stimulation. Type A and B lactic acidosis can be distinguished by the blood lactate/pyruvate ratio. Our objectives are to 1) investigate the incidence of hyperlactatemia and lactic acidosis in children with acute severe asthma, and 2) determine whether lactate elevation is type A or B. DESIGN: Prospective observational study. SETTING: University-affiliated tertiary care children's hospital. PATIENTS: All children (n = 105) with acute severe asthma admitted to the pediatric intensive care unit between May 1, 2008 and November 30, 2009 were included. INTERVENTIONS: Blood lactate concentration was measured on a blood gas analyzer for all blood gas assessments obtained for clinical care. Hyperlactatemia was defined as lactate >2.2 mmol/L and lactic acidosis as lactate >5 mmol/L and pH <7.35. If lactate concentration was >5 mmol/L, consent was requested for measuring blood lactate and pyruvate using enzymatic laboratory methods. Lactate/pyruvate ratio >25:1 indicated type A lactic acidosis. MEASUREMENTS AND MAIN RESULTS: Eighty-seven (83%) children had lactate >2.2 mmol/L and 47 (45%) had lactate >5 mmol/L. Of those with lactate >5 mmol/L, 33 (70%) had corresponding blood pH <7.35. Lactate/pyruvate ratios were obtained for 16 patients. Of these, lactate/pyruvate ratio was <10 in three patients; 10-25 in 11; >25 in one; and indeterminate in one. CONCLUSIONS: Lactic acidosis is common in children with acute severe asthma and is primarily type B occurring in the presence of normal oxygen delivery.

Measured degree of dehydration in children and adolescents with type 1 diabetic ketoacidosis.

OBJECTIVE: Successful management of diabetic ketoacidosis depends on adequate rehydration while avoiding cerebral edema. Our objectives are to 1) measure the degree of dehydration in children with type 1 diabetes mellitus and diabetic ketoacidosis based on change in body weight; and 2) investigate the relationships between measured degree of dehydration and clinically assessed degree of dehydration, severity of diabetic ketoacidosis, and routine serum laboratory values. DESIGN: Prospective observational study. SETTING: University-affiliated tertiary care children's hospital. PATIENTS: Sixty-six patients <18 yrs of age with type 1 diabetic ketoacidosis. INTERVENTIONS: Patients were weighed using a portable scale at admission; 8, 16, and 24 hrs; and daily until discharge. Measured degree of dehydration was based on the difference between admission and plateau weights. Clinical degree of dehydration was assessed by physical examination and severity of diabetic ketoacidosis was assessed by blood gas values as defined by international guidelines. Laboratory values obtained on admission included serum glucose, urea nitrogen, sodium, and osmolality. MEASUREMENTS AND MAIN RESULTS: Median measured degree of dehydration was 5.2% (interquartile range, 3.1% to 7.8%). Fourteen (21%) patients were clinically assessed as mild dehydration, 49 (74%) as moderate, and three (5%) as severe. Patients clinically assessed as moderately dehydrated had a greater measured degree of dehydration (5.8%; interquartile range, 3.6% to 9.6%) than those assessed as mildly dehydrated (3.7%; interquartile range, 2.3% to 6.4%) or severely dehydrated (2.5%; interquartile range, 2.3% to 2.6%). Nine (14%) patients were assessed as mild diabetic ketoacidosis, 18 (27%) as moderate, and 39 (59%) as severe. Diabetic ketoacidosis severity groups did not differ in measured degree of dehydration. Variables independently associated with measured degree of dehydration included serum urea nitrogen and sodium concentration on admission. CONCLUSION: Hydration status in children with diabetic ketoacidosis cannot be accurately assessed by physical examination or blood gas values. Fluid therapy based on maintenance plus 6% deficit replacement is reasonable for most patients.

Relative deficiency of arginine vasopressin in children after cardiopulmonary bypass.

OBJECTIVE: To describe changes in plasma arginine vasopress in concentration in children following cardiopulmonary bypass and determine whether, in some patients, plasma arginine vasopressin remains relatively low despite hemodynamic instability. DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit at a tertiary care university hospital. PATIENTS: One hundred twenty patients ≤ 18 yrs of age undergoing open heart surgery requiring cardiopulmonary bypass at Children's Hospital of Michigan between January 2008 and January 2009. INTERVENTIONS: Blood samples were collected before cardiopulmonary bypass and 4, 24, and 48 hrs after cardiopulmonary bypass for measurement of plasma arginine vasopressin concentration. MEASUREMENTS AND MAIN RESULTS: Mean plasma arginine vasopressin (pg/mL) for all patients was 21 ± 63 before cardiopulmonary bypass and 80 ± 145, 43 ± 79, and 19 ± 25 at 4, 24, and 48 hrs, respectively, after cardiopulmonary bypass. Patients with plasma arginine vasopressin below the lower quartile (< 9.2 pg/mL) at 4 hrs after cardiopulmonary bypass (n = 29), labeled group A, were examined separately and compared with the rest of the study population, labeled group B. Mean plasma arginine vasopressin was 4.9 ± 2.6 in group A at 4 hrs after cardiopulmonary bypass, statistically unchanged from its baseline mean plasma arginine vasopressin of 5.0 ± 10.4 (p = .977). Mean plasma arginine vasopressin in group B was 104 ± 160 at 4 hrs after cardiopulmonary bypass. Mean plasma arginine vasopressin of group A was also significantly lower as compared with group B before and 24 and 48 hrs after cardiopulmonary bypass. Hemodynamics, inotrope score, and serum sodium did not differ between groups at any time point. Plasma arginine vasopressin was measured immediately before exogenous arginine vasopressin administration in 10 patients; only those (n = 3) with hemodynamic instability and relatively low plasma arginine vasopressin concentration (< 9.2 pg/mL) had notable hemodynamic improvement. CONCLUSIONS: In some children undergoing open heart surgery, plasma arginine vasopressin concentration is relatively low at baseline and remains low after cardiopulmonary bypass regardless of hemodynamic stability and serum osmolality. These children are likely the optimal candidates for exogenous arginine vasopressin should hemodynamic compromise occur.

Infantile iron poisoning: challenges in diagnosis and management.

OBJECTIVE: To describe the clinical course and treatment of an infant with iron poisoning. DESIGN: Case report. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENT, INTERVENTION, AND RESULTS: A 7-week-old, ex-28-week premature infant, was accidentally poisoned with ferrous sulfate. She recovered completely from metabolic acidosis and shock after treatment with inotropes and chelation with deferoxamine, but her management was complicated by challenges of physiologic immaturity of developing organs. This is the youngest infant reported, to date, with iron poisoning resulting in metabolic acidosis and shock. CONCLUSIONS: This case illustrates the importance of including toxic exposure in the differential diagnosis of neonatal shock of unknown etiology. Because of physiologic immaturity, iron poisoning in young infants poses special diagnostic and therapeutic challenges.

Lessons learned in the life of a pediatric intensivist.

The metamorphosis from a medical student to a professor is a complex process. It involves not only the acquisition of new knowledge but also the impact of countless human interactions throughout one's life. By necessity therefore, this evolution is a never ending process of enrichment of the mind and the soul. An important contributor to this process is learning from the perspectives developed by others based on their experiences. I describe seven valuable lessons learned during my life that may be helpful to the developing pediatric intensivists.

Arginine vasopressin to manage hypoxemic infants after stage I palliation of single ventricle lesions.

OBJECTIVE: Management of patients with single ventricle physiology following stage I palliation procedures is often challenging, with optimization of the ratio of pulmonary-to-systemic blood flow as an important goal. Persistent hypoxemia may be a manifestation of elevated pulmonary vascular resistance and therefore decreased blood flow to the lungs. In such situations, the use of arginine vasopressin to increase systemic vascular resistance may be an effective strategy to improve pulmonary blood flow and maintain adequate pulmonary-to-systemic blood flow ratio. We describe three infants in whom persistent hypoxemia improved after institution of arginine vasopressin. DESIGN: Retrospective chart review. SETTING: Twenty-four bed medical-surgical pediatric intensive care unit at a large tertiary care academic hospital. PATIENTS: Three neonates with single ventricle physiology who received arginine vasopressin in the setting of hypoxemia following stage I palliation. RESULTS: Arginine vasopressin was initiated in all three patients for hypoxemia with a goal to increase systemic vascular resistance and generate a higher driving pressure for pulmonary blood flow. Twelve hours after arginine vasopressin initiation, systemic arterial saturation as determined by pulse oximetry and blood pressure increased, whereas heart rate, inotrope score, and Fio2 decreased in all three patients. Urine output was maintained and arterial lactate decreased during this time. Pulmonary-to-systemic flow ratio increased in one patient in whom it could be determined. CONCLUSION: In patients with single ventricle physiology and persistent hypoxemia following stage I palliation, administration of arginine vasopressin could improve oxygenation possibly by increasing systemic vascular resistance and therefore the pulmonary blood flow.

Metabolic acidosis as an underlying mechanism of respiratory distress in children with severe acute asthma.

OBJECTIVE: 1) To alert the clinician that increasing rate and depth of breathing during treatment of acute asthma may be a manifestation of metabolic acidosis with hyperventilation rather than worsening airway obstruction; and 2) to describe the frequency of metabolic acidosis with hyperventilation in children with severe acute asthma admitted to our pediatric intensive care unit. DESIGN: Retrospective medical record review. SETTING: University-affiliated children's hospital. PATIENTS: All patients admitted to the pediatric intensive care unit with a diagnosis of asthma between January 1, 2005, and December 31, 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-three patients with asthma (median age 7.8 yrs, range 0.7-17.9 yrs; 35 [66%] male; 46 [87%] black and 7 [13%] white) were admitted to the pediatric intensive care unit during the study period. Fifteen (28%) patients developed metabolic acidosis with hyperventilation (pH <7.35, Pco2 <35 torr [4.6 kPa], and base excess < or = -7 mmol/L) during their hospital course. Of these, lactic acid was assessed in four patients and was elevated in each; all had hyperglycemia (blood glucose >120 mg/dL [6.7 mmol/L]). Patients who developed metabolic acidosis with hyperventilation received asthma therapy similar to that received by patients who did not develop the disorder. Metabolic acidosis resolved contemporaneously with tapering of beta2-adrenergic agonists and administration of supportive care. All patients survived. CONCLUSIONS: Metabolic acidosis with hyperventilation manifesting as respiratory distress can occur in children with severe acute asthma. A pathophysiologic rationale exists for the contribution of beta2-adrenergic agents to the development of this acid-base disorder. Failure to recognize metabolic acidosis as the underlying mechanism of respiratory distress may lead to inappropriate intensification of bronchodilator therapy. Supportive care and tapering of beta2-adrenergic agents are recommended to resolve this condition.

Acute thiamine deficiency in diabetic ketoacidosis: Diagnosis and management.

OBJECTIVE: Persistent encephalopathy in a patient with diabetic ketoacidosis is often feared as a sign of cerebral edema. Although thiamine deficiency is a rare diagnosis in children, marginal nutritional status and osmotic diuresis may be risk factors. The objective was to describe a heretofore unreported cause of encephalopathy in a child with diabetic ketoacidosis and review the mechanisms and pathophysiology of thiamine deficiency in this clinical scenario. DESIGN: Case report and review of the literature. SETTING: Pediatric intensive care unit of a tertiary care pediatric hospital. PATIENT: A 13-yr-old girl. INTERVENTIONS: Treatment of dehydration and hyperglycemia, osmotherapy, and intravenous thiamine administration. MEASUREMENTS AND MAIN RESULTS: The patient presented with new-onset diabetes mellitus, severe diabetic ketoacidosis, and significant encephalopathy. Despite biochemical improvement with treatment of dehydration and hyperglycemia, her encephalopathy persisted. Computed tomography did not show cerebral edema and she showed no response to osmotherapy. Quantitative and functional assays revealed severe thiamine deficiency. The patient showed an immediate and dramatic response to intravenous thiamine administration. CONCLUSIONS: The clinical improvement as well as lab investigations suggests that thiamine deficiency was the cause of this child's encephalopathy. Because potential mechanisms exist for thiamine deficiency in diabetes mellitus and institution of insulin and glucose therapy may stress thiamine body stores, thiamine deficiency should be considered in children with diabetic ketoacidosis whose encephalopathy does not improve with improvement of biochemical status.