Clinical Features of COVID-19 in Patients with Congenital Central Hypoventilation Syndrome.

Background: The clinical course of COVID-19 in patients with congenital central hypoventilation syndrome (CCHS) is unknown. Methods: We conducted a cross-sectional questionnaire study in 43 patients with CCHS who had COVID-19. Results: The median age of patients was 11 [interquartile range (IQR) 6-22] years and 53.5% required assisted ventilation (AV) through tracheostomy. Disease severity ranged from asymptomatic infection (12%) to severe illness with hypoxemia (33%) and hypercapnia requiring emergency care/hospitalization (21%), increased AV duration (42%), increased ventilator settings (12%), and supplemental oxygen demand (28%). The median duration to return to baseline AV (n = 20) was 7 (IQR 3-10) days. Patients with polyalanine repeat mutations required increased AV duration compared with those with nonpolyalanine repeat mutations (P = 0.048). Patients with tracheostomy required increased oxygen during illness (P = 0.02). Patients aged ≥18 years took longer to return to baseline AV (P = 0.04). Conclusions: Our study suggests that all patients with CCHS should be vigilantly monitored during COVID-19 illness.

Perioperative outcomes and the effects of anesthesia in congenital central hypoventilation patients.

PURPOSE: Patients with congenital central hypoventilation syndrome (CCHS) have autonomic dysfunction and lack ventilatory responses to hypoxemia and hypercarbia and thus are prone to adverse events during general anesthesia. The objective of this study was to describe the perioperative outcomes of patients with CCHS who were undergoing diaphragm pacer (DP) implantation surgeries under general anesthesia. METHODS: A retrospective cohort study was conducted on patients with CCHS who underwent DP implantation surgeries at CHLA between January 2000 and May 2016. Charts were reviewed for demographics, PHOX2B genotype, ventilatory support, comorbidities, anesthesia administered, and perioperative courses. RESULTS: Of 19 patients with CCHS (58% female) mean age at surgeries was 8.6 ± 5.8 years. Seventeen patients were ventilator-dependent during sleep only; two were ventilator dependent 24 h per day. Mean surgery duration was 3.1 ± 0.5 h. Seventeen patients were extubated to PPV via tracheostomy in the OR. Two patients were extubated to NPPV on postoperative day (POD) 1. Mean transition time to home ventilator or NPPV was 3.0 ± 2.2 days, and mean hospital stay was 5.0 ± 2.1 days. One patient premedicated without ventilatory support developed hypoxemia and hypoventilation. Ten patients (52%) had intraoperative events such as bradycardia, hypotension, significant hypoxemia, and bronchospasm. Fifteen patients had postoperative events. Hypoxemia, pneumonia, and atelectasis accounted for most of perioperative complications. One patient experienced seizure on POD 2 due to hypercarbia. CONCLUSION: Patients with CCHS are vulnerable to the cardiorespiratory effects of sedative and anesthetic agents. Therefore, they require vigilant monitoring and optimal ventilatory support in the perioperative period.

Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

Rapid Response and Code Events in Hospitalized Children on Home Mechanical Ventilation.

BACKGROUND: There is limited knowledge of rapid-response (RR) events and code events for children receiving home mechanical ventilation (HMV) via a tracheostomy in a non-ICU respiratory care unit. The purpose of this study was to describe the demographic and clinical factors leading to deterioration among these children and to identify the incidence and outcomes following rapid-response and code events. METHODS: A retrospective review was conducted on hospitalized HMV children who had RR/code events in a non-ICU respiratory care unit. RESULTS: There were a total of 50 RR events, and the primary clinical problem was acute respiratory distress, with 27 subjects (54%) needing ventilator adjustments. Twenty (40%) RR events occurred among children who were awaiting initial home discharge. Of 18 total code events, 7 (39%) children needed a tracheostomy-related intervention. There were 10 (56%) codes among children on mechanical ventilation awaiting initial home discharge. Children on HMV had 8.73 RR events per 1,000 patient days, whereas all other hospitalized children had 4.61 RR events per 1,000 patient days. In addition, children on HMV had 3.14 codes per 1,000 patient days, whereas all other hospitalized children had 0.74 codes per 1,000 patient days. All children were discharged from the hospital, and no deaths were associated with RR/code events for the index hospitalization. CONCLUSIONS: The overall incidence of RR/code events in children on HMV was higher than among non-HMV hospitalized children. Children on HMV preparing for their initial hospital discharge had the greatest number of RR/code events. The most prevalent interventions among children with RR events were ventilator setting adjustments, and among children with codes the most frequent actions were tracheostomy-related interventions. Developing strategies to predict risk factors for RR/code events may help decrease harm among children on HMV.

Adult With PHOX2B Mutation and Late-Onset Congenital Central Hypoventilation Syndrome.

ABSTRACT: PHOX2B 20/27 polyalanine repeat mutation (PARM) in patients with congenital central hypoventilation syndrome (CCHS) is generally associated with full-time ventilator dependence, Hirschsprung disease, and increased risk for cardiac asystole. We follow a 14-year-old boy with CCHS PHOX2B 20/27 PARM who is full-time ventilator dependent via tracheostomy and has Hirschsprung disease. His mother, age 52 years, has a history of prolonged recovery from anesthesia and an elevated serum bicarbonate level of 45 mEq/L discovered on routine blood chemistry. PHOX2B gene mutation analysis was performed and showed an identical 20/27 PARM, diagnostic of CCHS. Late-onset CCHS has been reported in those with 20/24, 20/25 PHOX2B PARM, and in nonpolyalanine repeat mutations. This is the first report of a patient with PHOX2B 20/27 PARM with a mild phenotype diagnosed during adulthood. This unusual presentation supports the screening for PHOX2B mutations in parents of children with CCHS.

Congenital central hypoventilation syndrome: diagnosis and management.

INTRODUCTION: Congenital central hypoventilation syndrome (CCHS) is a rare disorder defined by a failure in autonomic control of breathing secondary to mutations of the PHOX2B gene. Affected individuals demonstrate absent or diminished physiologic response to hypercapnia and hypoxia that is most severe during sleep as well as multi-system dysregulation of autonomic functions. Areas covered: In this review, we will discuss how evaluation of the disease-defining PHOX2B gene aids diagnosis and helps prognosticate disease severity, review disease physiology, describe clinical presentation and various aspects of autonomic nervous system dysregulation, review ventilatory strategies, and highlight current challenges in the care of these complex patients. Expert commentary: CCHS is a rare disorder that requires a high degree of vigilance. PHOX2B mutation is essential for diagnosis and also helps direct disease management. There is currently no pharmacologic treatment proven effective in improving disease-related hypoventilation and care is focused on providing adequate ventilatory support and managing autonomic dysfunction.

Three-Generation Family With Congenital Central Hypoventilation Syndrome and Novel PHOX2B Gene Non-Polyalanine Repeat Mutation.

ABSTRACT: PHOX2B non-polyalanine repeat mutation (NPARM) in patients with congenital central hypoventilation syndrome (CCHS) is generally considered to be associated with full-time ventilator dependence and severe autonomic nervous system dysfunction. We report a three-generation family with four individuals possessing a novel PHOX2B NPARM (c.245C > T) with variable phenotypes. This mutation was inherited in an autosomal dominant pattern with variable penetrance. The affected family members with CCHS have a milder phenotype than is typically expected with a NPARM. Two family members are ventilator dependent only during sleep and do not have Hirschsprung disease or neural crest tumors. One family member was asymptomatic until systemic hypertension developed during adulthood and another family member remains asymptomatic as an adult. Our findings emphasize the importance of monitoring adults with a PHOX2B NPARM who are considered asymptomatic in childhood.

Congenital central hypoventilation syndrome: diagnostic and management challenges.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder with failure of central control of breathing and of the autonomic nervous system function due to a mutation in the paired-like homeobox 2B (PHOX2B) gene. Affected patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxemia, and they do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis of CCHS must be confirmed with PHOX2B gene mutation. Generally, the PHOX2B mutation genotype can aid in anticipating the severity of the phenotype. They require ventilatory support for life. Home assisted ventilation options include positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and diaphragm pacing via phrenic nerve stimulation, but each strategy has its associated limitations and challenges. Since all the clinical manifestations of CCHS may not manifest at birth, periodic monitoring and early intervention are necessary to prevent complications and improve outcome. Life-threatening arrhythmias can manifest at different ages and a normal cardiac monitoring study does not exclude future occurrences leading to the dilemma of timing and frequency of cardiac rhythm monitoring and treatment. Given the rare incidence of CCHS, most health care professionals are not experienced with managing CCHS patients, particularly those with diaphragm pacers. With early diagnosis and advances in home mechanical ventilation and monitoring strategies, many CCHS children are surviving into adulthood presenting new challenges in their care.

Thoracoscopic placement of phrenic nerve pacers for diaphragm pacing in congenital central hypoventilation syndrome.

PURPOSE: Congenital central hypoventilation syndrome (CCHS), or Ondine's curse, is a rare disorder affecting central respiratory drive. Patients with this disorder fail to ventilate adequately and require lifelong ventilatory support. Diaphragm pacing is a form of ventilatory support which can improve mobility and/or remove the tracheostomy from CCHS patients. Little is known about complications and long-term outcomes of this procedure. METHODS: A single-center retrospective review was performed of CCHS patients undergoing placement of phrenic nerve electrodes for diaphragm pacing between 2000 and 2012. Data abstracted from the medical record included operation duration, ventilation method, number of trocars required, and postoperative and pacing outcomes. RESULTS: Charts of eighteen patients were reviewed. Mean surgical time was 3.3±0.7 hours. In all cases except one, three trocars were utilized for each hemithorax, with no conversions to open procedures. Five patients (27.8%) experienced postoperative complications. The mean ICU stay was 4.3±0.5 days, and the mean hospital stay is 5.7±0.3days. Eleven patients (61.1%) achieved their daily goal pacing times within the follow-up period. CONCLUSIONS: Thoracoscopic placement of phrenic nerve electrodes for diaphragmatic pacing is a safe and effective treatment modality for CCHS. Observed complications were temporary, and the majority of patients were able to achieve pacing goals.

Examining pediatric emergency home ventilation practices in home health nurses: Opportunities for improved care.

OBJECTIVES: To assess the pediatric home health nurses' knowledge in tracheostomy and ventilator emergency care on home mechanical ventilation (HMV). BACKGROUND: Emergencies are frightening experiences for solo home health nurses and require advanced skills in emergency response and care, especially in pediatric patients who pose unique challenges. WORKING HYPOTHESIS: Nurses with greater years of nursing experience would perform better on emergency HMV case-based scenarios than nurses with less years of experience. STUDY DESIGN: An exploratory online survey was used to evaluate emergency case-based pediatric scenarios. Demographic and professional experiences were profiled. PATIENT-SUBJECT SELECTION: Seventy-nine nurses had an average of 6.73 (SD = 1.41) years in pediatric nursing. Over 70% received their HMV training in their agency, 41% had less than 4 years of experience, and 30.4% had encountered at least one emergency situation at home. METHODOLOGY: The online survey was distributed by managers of 22 home health agencies to nurses providing pediatric HMV care. RESULTS: Nurses scored an average of 4.87 out of 10 possible points. There were no significant differences between nurses with <4 years of experience versus those with more experience on ventilator alarms knowledge or total knowledge. Ninety-seven percent of the nurses favored more training in HMV from a variety of settings (e.g., agency, on-line training). CONCLUSIONS: Nurses did not perform well in case-based ventilator alarm scenarios. Length of nursing experience did not differentiate greater knowledge. It is clear that nurses require and want more training in emergency-based HMV. Recommendations for an enhanced curriculum are suggested.

End-of-life discussions and advance care planning for children on long-term assisted ventilation with life-limiting conditions.

Families of children with life-limiting conditions who are on long-term assisted ventilation need to undertake end-of-life advance care planning (ACP) in order to align their goals and values with the inevitability of their child's condition and the risks it entails. To discuss how best to conduct ACP in this population, we performed a retrospective analysis of end-of-life discussions involving our deceased ventilator-assisted patients between 1987 and 2009. A total of 34 (72 percent) of 47 study patients were the subject of these discussions; many discussions occurred after acute deterioration. They resulted in directives to forgo or limit interventions for 21 children (45 percent). We surmise that many families were hesitant to discuss end-of-life issues during periods of relative stability. By offering anticipatory guidance and encouraging contemplation of patients' goals both in times of stability and during worsening illness, health care providers can better engage patients' families in ACP. As the child's condition progresses, the emphasis can be recalibrated. How families respond to such encouragement can also serve as a gauge of their willingness to pursue ACP.

Hospital readmissions for newly discharged pediatric home mechanical ventilation patients.

BACKGROUND: Ventilator-dependent children have complex chronic conditions that put them at risk for acute illness and repeated hospitalizations. OBJECTIVES: To determine the 12-month incidence of and risk factors for non-elective readmission in children with chronic respiratory failure (CRF) after initiation on home mechanical ventilation (HMV) via tracheostomy. METHODS: A retrospective cohort study of 109 HMV patients initiated and followed at an university-affiliated children's hospital between 2003 and 2009. Patient characteristics are presented using descriptive statistics; generalized estimated equations are used to estimate adjusted odds ratios of select predictor variables for readmission. RESULTS: The 12-month incidence of non-elective readmission was 40%. Close to half of these readmissions occurred within the first 3 months post-index discharge. Pneumonia and tracheitis were the most common reasons for readmission; 64% were pulmonary- or tracheostomy-related. Most demographic and clinical patient characteristics were not statistically associated with non-elective readmissions. Although, a change in the child's management within 7 days before discharge was associated readmissions shortly after index discharge. CONCLUSION: Non-elective readmissions of newly initiated pediatric HMV patients were common and likely multifactorial. Many of these readmissions were airway-related, and some may have been potentially preventable.

Costs of hospitalized ventilator-dependent children: differences between a ventilator ward and intensive care unit.

Hospitalizing clinically stable patients in critical care settings results in unnecessary healthcare costs and thwarts timely patient throughput. Some pediatric hospitals care for their stable ventilator-dependent children outside of pediatric intensive care units (PICUs). To date, no analysis of the costs of these pediatric ventilator units compared to PICUs has been performed. We conducted a retrospective comparison of PICU and ventilator ward costs of hospitalizations for 103 admissions in which ventilator-dependent children served as their own matched controls between 2004 and 2007. For included admissions, patients were hospitalized in both units during the same admission and spent more than 1 day in their initial unit. Comparisons of costs were made using the last full PICU day and first full ward day. For the study period, the mean PICU cost of hospitalization per day was $3,565 (standard deviation [SD] ± 716.50). The mean ward cost was $2,052 (SD ± 617). The mean PICU cost was significantly larger than the mean ward cost (paired t-test, P < 0.0001). Ventilator ward total and variable costs were significantly less than those in the PICU, and such units represent a potential cost saving measure for hospitals that care for ventilator-dependent children.

Outcomes and causes of death in children on home mechanical ventilation via tracheostomy: an institutional and literature review.

OBJECTIVE: To describe outcomes and causes of death in children on chronic positive-pressure ventilation via tracheostomy. STUDY DESIGN: We conducted a retrospective observational cohort analysis of 228 children enrolled in an university-affiliated home mechanical ventilation (HMV) program over 22 years (990 person-years). Cumulative incidences of survival and liberation from HMV are presented. Time-to-events were compared by reason for chronic respiratory failure (CRF) and age and date of HMV initiation with Kaplan-Meier and Cox regression analyses. Circumstances of death are described. RESULTS: Of our cohort, 47 of 228 children died, and 41 children were liberated from HMV. The 5-year cumulative incidences of survival and liberation were 80% and 24%, respectively. Being placed on HMV for chronic pulmonary disease was independently associated with liberation from HMV (hazard ratio, 7.38; 95% CI, 3.0-18.2; P < .001). Neither age nor reasons for CRF were associated with shortened survival. Progression of underlying condition accounted for only 34% of deaths; 49% of deaths were unexpected. CONCLUSION: Most children on HMV survive or were weaned off. However, a sizable number of children in our cohort died, and many deaths were unexpected and from causes not directly related to their primary reason for CRF.

Children with corrected or palliated congenital heart disease on home mechanical ventilation.

Infants and children with surgically corrected or palliated congenital heart disease (CHD) are at risk for chronic respiratory failure, necessitating home mechanical ventilation (HMV) via tracheostomy. However, very little data exists on this population or their outcomes. We conducted a retrospective chart review of all children with CHD enrolled in the Childrens Hospital Los Angeles HMV program between 1994 and 2009. Data were collected on type of heart lesion, surgeries performed, number of failed extubations, timing of tracheostomy, mortality, length of time on HMV, weaning status, associated co-morbidities, and Risk Adjusted classification for Congenital Heart Surgery (RACHS-1) category. Thirty-five children were identified; six with single ventricle anatomy, who received palliative procedures. Twenty-three (66%) patients are alive; 8 (23%) living patients have been weaned off HMV. Twelve (34%) patients are deceased. The incidence of mortality for single ventricle patients was 50%, and only one of the surviving children has received final palliation and weaned off HMV. Eight of nine patients (89%) with a RACHS score > or =4 died, and none have been weaned off of HMV. The 5-year survival for all CHD HMV patients was 68%; 90% for patients with RACHS < or =3; and 12% for patients with score > or =4. Children with more complex lesions, as demonstrated by single ventricle physiology or greater RACHS scores, had higher mortality rates and less success weaning off HMV. This case series suggests that caregivers should give serious consideration to the type of heart defect as they advise families considering HMV in children with CHD.

How much do primary care givers know about tracheostomy and home ventilator emergency care?

UNLABELLED: Children on home mechanical ventilation are a high-risk population. How much do primary caregivers (PC) know about handling unexpected situations with tracheostomies or malfunction of their ventilators? To answer this, we prospectively studied the knowledge of 152 PC (108 parents and 44 nurses), using a 25-question survey regarding emergency situations at home. RESULTS: their mean score was 20.2 correct answers (81%). However, 96 PC (63%) did not know that the low pressure ventilator alarm would not sound if the tracheostomy tube decannulated while still connected to the ventilator. Seventy-nine PC (52%) failed to understand high pressure alarms sound and mucous plugging. Sixty-six PC (43%) did not know how much power a battery stored after the suction machine was fully charged. Sixty-one PC (40%) did not know when the low pressure or low minute volume alarm sounds. Fifty-six PC (37%) relied on the ventilator alarm to determine the presence of mucous plugs. There were no significant differences in the scores of PC who used continuous flow ventilators, nor in English-speaking PC versus Spanish-speaking PC. The experience of the PC did not make a difference in their knowledge of HMV emergency care. Having professional training did not pose an advantage in the score for nurses. We conclude that most PC had a good understanding of emergency care. We speculate that more in depth education on the technical aspects of ventilator alarms and tracheal mucous plugging may help to reduce or prevent emergencies of children on HMV.

Do sequential chest radiographs prompt changes in therapy for home mechanical ventilation children admitted for pneumonia?

How many chest radiographs prompt changes in therapy for home mechanical ventilation (HMV) patients admitted to the hospital for pneumonia? Since HMV patients are more complex than those with simple community-acquired pneumonia, it is not known how many chest radiographs are needed for optimal management. To answer this, we reviewed all HMV patients admitted for pneumonia from July 2007 through June 2008. Demographic data, sequential chest radiographs, and changes in respiratory orders within 24 hours were recorded Childrens Hospital Los Angeles followed 180 HMV patients. Twenty-eight patients (16%) were admitted (36 readmissions). Twenty-five of these patients (90%) required full-time HMV Eighteen patients (64%) had the diagnosis of chronic lung disease. On discharge, 24 patients (66%) had residual pneumonia on chest radiographs. We conclude that HMV patients averaged five chest radiographs per pneumonia admission. Two-thirds of the chest radiographs did not prompt subsequent changes in respiratory therapy. More than one-third of the chest radiographs found no interval changes. The majority of discharges were not contingent on resolution of the chest radiographs findings. We speculate that the frequency of chest radiographs could be less and that chest radiographs were not the sole predictors of changes in respiratory treatment or the decision to discharge.

Congenital hypoventilation syndromes.

Although rare, congenital hypoventilation syndromes profoundly impact affected patients and families. In some diseases, such as congenital central hypoventilation syndrome (CCHS), hypoventilation is a key presenting feature. Ventilatory abnormalities may not be immediately evident in other disease states. The clinical aspects of several pediatric hypoventilation syndromes, including CCHS, Chiari type II malformation, Prader-Willi syndrome, familial dysautonomia, and rapid onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation are presented.

Initiation of home mechanical ventilation in children with neuromuscular diseases.

OBJECTIVE: To determine how often home mechanical ventilation (HMV) is instituted electively in children with respiratory failure from neuromuscular diseases and whether there were opportunities to discuss therapeutic options with patients/families before respiratory failure. METHODS: Patients with neuromuscular disease (n = 73) requiring HMV (age, 2 months to 24 years) were studied. Whether HMV was initiated nonelectively because of acute respiratory failure or electively before acute respiratory failure, and opportunities for health care providers to discuss therapeutic options with patients/families before acute respiratory failure (hospitalization with pneumonia, clinic visits for preoperative evaluation, pulmonary function testing [PFT] and/or polysomnography [PSG]) were recorded. RESULTS: HMV was initiated electively in 21% of patients with neuromuscular disease; 69% of the nonelective HMV group had HMV initiated after respiratory failure caused by pneumonia. In the nonelective group, opportunities for discussion of therapeutic options with the patients and families could have occurred before respiratory failure during 111 hospitalizations for pneumonia, 13 preoperative evaluations, 43 abnormal PFTs, and 24 abnormal PSGs. CONCLUSIONS: Most patients with neuromuscular disease had HMV initiated nonelectively after acute respiratory failure caused by pneumonia. Opportunities for discussing the therapeutic options with patients and families before respiratory failure were missed or ineffective.

Mother-daughter transmission of congenital central hypoventilation syndrome.

The cause of congenital central hypoventilation syndrome (CCHS) is unknown, but a genetic etiology is strongly suspected. We report a 25-year-old woman with CCHS (no Hirschsprung's disease) who gave birth to a daughter who also has CCHS. This suggests a dominant mode of inheritance for CCHS in this family. Pregnancy can be associated with physiologic challenges in CCHS. The increase in endogenous progesterone may stimulate breathing and may possibly improve symptoms of hypoventilation. Although this patient did not have any worsening in symptoms, her hyperoxic hypercapnic rebreathing ventilatory response was not different when pregnant versus when not pregnant. Ventilatory support for the patient was successfully managed with diaphragm pacing throughout the pregnancy without the need to adjust settings, despite the enlarged abdomen during pregnancy. We conclude that CCHS may be an inherited disorder. Increased endogenous progesterone during pregnancy has no effect on the ventilatory response, and diaphragm pacing can successfully provide adequate ventilation throughout pregnancy.