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Biomedical subjects

Thomas G Keens

Publications and source records attributed to Thomas G Keens.

At least 19 recordsLinked to original sources

Alcohol use in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) is a rare disorder where there is failure of automatic control of breathing. With improved recognition of CCHS, more children are appropriately diagnosed and treated in infancy, allowing survival into adult years. Because most of these children are able to participate in regular school, they are exposed to common adolescent behaviors, such as abusing alcohol and drugs. Alcohol and many illicit substances are known respiratory depressants. We report on 3 cases of adolescents/young adults with CCHS who had severe adverse events related to alcohol, including coma and death. This series illustrates the dangers of alcohol abuse in CCHS. We speculate that adolescents with CCHS may be less able to perceive the risks of substance abuse and impulsive behavior, leading to increased morbidity and mortality. Patients with CCHS appear to lack anxiety and the awareness that their inability to perceive physiologically dangerous levels of hypercarbia and hypoxia deprives them of important protective mechanisms.

Adolescent↗

The effect of scoliosis surgery on lung function in the immediate postoperative period.

STUDY DESIGN: Prospective, single-cohort study. OBJECTIVES: To determine the immediate change in pulmonary function test (PFT) in children following scoliosis surgery. SUMMARY OF BACKGROUND DATA: The number of pediatric scoliosis surgeries is increasing each year because of recent advances in spinal instrumentation, surgical techniques, and improved perioperative monitoring. Pulmonary function decreases immediately following scoliosis surgery, but the extent of this decrease is not well documented in pediatric patients. To use preoperative PFTs to assess the risk of postoperative complications, knowledge of the postoperative decline in PFT is necessary. METHODS: We measured preoperative and daily postoperative PFT in 24 children who had scoliosis surgery (age 12.7 +/- 2.7 [SD] years) from January 2002 to June 2003. There were 10 male and 14 female patients. Two (8%) patients had congenital scoliosis, 11 (46%) had idiopathic scoliosis, 9 (38%) had scoliosis due to a neuromuscular disease, and 2 (8%) had kyphoscoliosis. Fifteen (62%) patients had posterior spinal fusion (PSF), 5 (21%) had anterior spinal fusion (ASF), and 4 (17%) had both ASF and PSF performed. PFT parameters (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], FEV1/FVC, and forced expiratory rate between 25% and 75% of FVC [FEF25%-75%]) were measured before surgery and daily after surgery by bedside spirometry until hospital discharge. RESULTS: PFT declined up to 60% after surgery. The PFT nadir is at 3 days. PFT values remained significantly decreased at 1 week, with values at about half of preoperative baseline. No patient required postoperative mechanical ventilation > or =3 days. There was no statistical significance between the degree of decline in PFT with etiology of either the scoliosis or the type of surgery performed. CONCLUSIONS: Our study found that patients are still at risk for postoperative complications as long as 1 week postoperatively and that PFTs do not return to near baseline until 1 to 2 months after surgery. The postoperative decrease in PFT should be considered during preoperative prediction of postoperative risk.

Adolescent↗

Neuroanatomic deficits in congenital central hypoventilation syndrome.

Congenital Central Hypoventilation Syndrome (CCHS) patients exhibit compromised autonomic regulation, reduced breathing drive during sleep, diminished ventilatory responses to chemoreceptor stimulation, and diminished air hunger perception. The syndrome provides an opportunity to partition neural processes regulating breathing and cardiovascular action. No obvious lesions appear with conventional magnetic resonance imaging; however, T2 relaxometry procedures can detect reduced cell or fiber density or diminished myelination not found with routine evaluation. High-resolution T1, proton density, and T2-weighted brain images were collected from 12 patients and 28 age- and gender-matched controls. Voxel-by-voxel T2 maps were generated from the proton density and T2-weighted images and evaluated by voxel-based-relaxometry procedures. Normalized and smoothed T2 maps were compared between groups using analysis of covariance at each voxel, with age and ventricle size included as covariates. Patients showed damaged or maldeveloped tissue, principally right-sided, including white matter from the level of the anterior cingulate cortex caudally to the level of the posterior cingulate and laterally to the posterior superior temporal cortex. Portions of the posterior, mid, and anterior cingulate, as well as the internal capsule, putamen, and globus pallidus and basal forebrain extending to the anterior and medial thalamus were affected. Deficits in the cingulum bundle and mid-hippocampus and ventral prefrontal cortex appeared, as well as the right cerebellar cortex and deep nuclei. Neuroanatomic deficiencies in limbic structures suggest a structural basis for reduced air hunger perception, thermoregulatory and autonomic deficiencies in the syndrome, while cerebellar deficits may also contribute to breathing and cardiovascular dysregulation.

Adolescent↗

Aberrant neural responses to cold pressor challenges in congenital central hypoventilation syndrome.

Patients with congenital central hypoventilation syndrome (CCHS), a condition characterized by impaired ventilatory responses to chemoreceptor stimulation, do not show the normal increase in respiratory rate and respiratory-related heart rate variation to cold forehead stimulation, a challenge that bypasses central chemoreceptors. We hypothesized that a forehead cold pressor challenge would reveal abnormal neural response patterns, as assessed by functional magnetic resonance imaging, in brain regions that are responsible for the integration of cold afferent stimulation with respiratory and cardiovascular output in patients with CCHS. Primary sensory thalamic and cortical areas for the forehead showed diminished responses in 13 patients with CCHS (ventilator dependent during sleep but not waking, no Hirschsprung's disease) compared with 14 control subjects, despite initial signal changes in the cortex being similar in both groups. Cerebellar cortex and deep nuclei; basal ganglia; and middle to posterior cingulate, insular, frontal, and temporal cortices showed reduced signal rises in patients with CCHS. Areas within the frontal and anterior cingulate cortices exhibited marked signal declines in control subjects but little change in patients with CCHS. No response occurred in either group in the dorsal medulla, but medial and ventral medullary areas showed enhanced signals in patients with CCHS. The cold pressor stimulation did not recruit dorsal medullary sites that would be affected by PHOX2B (a mutation of which is associated with the syndrome) expression in either group but demonstrated deficient cerebellar and medial medullary influences that, by action on rostral sites, may underlie the loss of respiratory responses.

Adolescent↗

FMRI responses to hyperoxia in congenital central hypoventilation syndrome.

Congenital Central Hypoventilation Syndrome (CCHS) patients show partial retention of peripheral chemoreception despite impaired ventilatory responses to CO2 and hypoxia. The condition allows examination of central responses to hyperoxia, which minimizes afferent traffic from peripheral chemoreceptors. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals over the brain during a baseline and subsequent 2-min hyperoxia (100% O2) period in 14 CCHS and 15 control subjects. After partitioning gray matter and correcting for global effects, the images were analyzed using volume-of-interest time trends followed by repeated-measures ANOVA and conventional cluster analyses. Respiratory rates initially (first 20 s) fell in CCHS, but rose in control subjects; CCHS heart rate increased in the first minute, and then decreased in the second minute, as in controls, but with muted rise and extent of decline. Multiple sites within the cerebellum, midbrain, and pons responded similarly to the challenge in both groups. Response patterns differed early in the right amygdala, paralleling initial respiratory pattern deficits, and late in the right insula, concomitant with cardiac rate differences. Signals also differed between groups in the medial and anterior cingulate, hippocampus, head of caudate, and lentiform nuclei, as well as pontine and midbrain structures and regions within the superior temporal and inferior frontal cortical gyri. The findings emphasize that structures that can alter respiratory timing, such as the amygdala, and modulate sympathetic outflow, such as the right insula, are deficient in CCHS. Medullary and pontine areas targeted by PHOX2B expression are also affected.

Adolescent↗

Disordered respiratory control in children with partial cerebellar resections.

While the cerebellum is not traditionally thought of as having an important role in respiratory control, breathing involves cyclic motor acts that require cerebellar coordination. We postulate that children with partial cerebellar resections have disordered respiratory control due to altered synchronization of ventilatory muscles. We reviewed the records of 36 children following partial cerebellar resections due to neoplasms confined to the cerebellum. P aCO2 values were elevated in 19% of patients. Six patients had apneic or bradypneic events documented within the first month after resection. Two patients required intubation with assisted ventilation, and one needed assisted ventilation for 7.3 weeks. Those with apnea had lower oxygen saturations, and a longer need for supplemental oxygen. Patients with apnea were older than those without apnea. Swallowing, which uses many of the same muscles as those needed to maintain upper airway patency, was dysfunctional in 50% of those with apneas. We conclude that children with cerebellar resections have an increased incidence of apnea, hypoventilation, and hypoxemia not otherwise explained by pulmonary disease, and some require prolonged assisted ventilation. We speculate that these abnormalities are manifestations of altered respiratory control caused by dysfunctional cerebellar coordination of ventilatory muscles.

Apnea↗

Preoperative predictors of prolonged postoperative mechanical ventilation in children following scoliosis repair.

Scoliosis is associated with progressive restrictive lung disease and an increased risk of pulmonary complications following surgical correction. Identification of higher risks for prolonged postoperative mechanical ventilation (MV) improves postoperative care. Our objective was to determine if preoperative pulmonary function tests (PFT) predict prolonged postoperative MV (defined as MV >or=3 days). We correlated preoperative PFT (forced expired volume in 1 sec, FEV1; vital capacity, VC; inspiratory capacity, IC; maximal inspiratory pressure, MIP; total lung capacity, TLC; and residual volume, RV) and postoperative MV days in 125 patients who had scoliosis surgery (aged 13.7 +/- 3.0 (SD) years) from January 1990-July 2001. We had 71 male and 54 female patients. Scoliosis types were 13 congenital, 27 idiopathic, 57 neuromuscular, 23 syndrome/tumor, and 5 kyphoscoliosis. Forty patients (32%) had postoperative MV >or=3 days. Independent factors likely requiring postoperative MV >or=3 days were neuromuscular scoliosis (P < 0.001) and FEV1 <40% predicted. Independent factors most likely were: neuromuscular scoliosis with preoperative FEV1 <40% predicted (P < 0.01). Independent factors most unlikely were: idiopathic scoliosis (P < 0.002). VC <60% predicted, IC <30 ml/kg, TLC <60% predicted, and MIP <60 cm H2O correlated with postoperative MV >or=3 days (P < 0.05). We found no association between RV and postoperative MV. FEV1 <40% predicted, VC <60% predicted, IC <30 ml/kg, TLC <60% predicted, MIP <60 cm H2O, and neuromuscular disease each correlated with prolonged postoperative MV. Neuromuscular disease or a preoperative FEV(1) <40% predicted were more likely, and older children with neuromuscular disease and FEV1 <40% predicted were most likely to require prolonged postoperative MV (P < 0.01). Clearly FEV1, and possibly VC, IC, TLC, and MIP, may increase accuracy in predicting the need for prolonged postoperative MV.

Adolescent↗

Diaphragm pacers as a treatment for congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome is a rare syndrome present from birth, and is defined as the failure of automatic control of breathing. All patients with congenital central hypoventilation syndrome require life-long ventilatory support during sleep, although approximately a third of patients require ventilatory support 24 h per day. Diaphragm pacers offer a modality of ventilatory support that affords congenital central hypoventilation syndrome patients with maximal mobility for full-time ventilatory patients, and they may allow for a more normal lifestyle in the appropriate patient. They may permit tracheostomy decannulation in those requiring only support during sleep. Diaphragm pacing entails surgical placement of an electrode onto the phrenic nerve, connected to a subcutaneous receiver. There is an external battery-operated transmitter and antenna placed on the skin over the receiver. The transmitter emits energy, similar to radio transmission, which is converted into an electrical current by the receiver. This stimulates the phrenic nerve resulting in a diaphragmatic contraction. Settings on the transmitter include respiratory rate and electrical voltage, and are adjusted to give enough tidal volume to allow for adequate oxygenation and ventilation. Therefore, diaphragm pacing is an attractive alternative mode of mechanically assisted ventilation for many patients with congenital central hypoventilation syndrome.

Diaphragm↗

Temporal trends of cardiac and respiratory responses to ventilatory challenges in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients exhibit respiratory deficits to ventilatory challenges, diminished breathing drive during sleep, and reduction of respiratory-related heart rate variation, but at least partially preserved peripheral chemoreception. We hypothesized that integration of afferent activity with respiratory motor output is deficient in CCHS, rather than chemoreceptor failure, and that examination of trends in heart and breathing rates and variabilities following ventilatory challenges may clarify the deficient mechanisms. Twelve children with CCHS and 12 age- and gender-matched control cases were subjected to hyperoxic hypercapnic, poikylocapnic hypoxic, and hyperoxic challenges while supine. Heart and respiratory rates and variabilities during 60-s baseline and 120-s challenge periods were assessed. Hypoxia and hypercapnia enhanced breathing rate in control subjects; in CCHS cases, the rise differed during hypercapnia and did not occur to hypoxia. Hyperoxia showed initial transient patterns in breathing rate that differed between groups. A heart rate increase to hypoxia and late decline to hyperoxia were muted in CCHS patients. In hypercapnia, heart rate followed similar rising patterns in both groups. Overall CCHS heart rate variability was lower in baseline and challenge periods, principally due to diminished respiratory-related variation, especially during hypercapnia. No heart rate variability group differences emerged in hypoxia, and only a late increase for CCHS cases developed in hyperoxia. The findings indicate retention of aspects of chemoreceptor sensitivity in CCHS cases. The heart rate alterations to ventilatory challenges suggest specific compensatory responses of a slower nature remain intact in CCHS, whereas other rapidly changing components are deficient.

Adolescent↗

Preoperative polysomnograms and infant pulmonary function tests do not predict prolonged postoperative mechanical ventilation in children following scoliosis repair.

Our objective was the identification of children with scoliosis at higher risk of prolonged postoperative mechanical ventilation (MV) permits improved pre- and perioperative respiratory care to reduce postoperative complications. Pulmonary function testing (PFT) predicts prolonged postoperative MV in children who can reliably perform PFT, but some children cannot perform PFT. The objective of this study was to determine if polysomnography (PSG) or infant pulmonary function testing (IPFT) could predict prolonged postoperative MV (defined as MV >3 days) in children undergoing scoliosis surgery who could not reliably perform PFT. We studied 110 patients (age range, 10.8 +/- 4.9 [SD] years) who had preoperative PSG, and 18 patients (age range, 4.0 +/- 2.9 [SD] years) who had preoperative IPFT prior to undergoing any type of scoliosis repair by the Children's Hospital of Los Angeles Division of Orthopedic Surgery from January 1990- July 2001. The following information was reviewed and correlated: preoperative PSG parameters (baseline and nadir S(aO(2) ), baseline and peak P(ETCO(2) ), and apnea hypopnea index [AHI]), preoperative IPFT parameters (respiratory system compliance [C(rs)], respiratory system resistance [R(rs)], tidal volume [V(T)], and FRC), and length of postoperative MV. Twenty-seven patients (25%) who had PSG and 5 patients (28%) who had IPFT required postoperative MV >3 days. There was no association between baseline and nadir S(aO(2) ) <or= 92%, baseline and peak P(ETCO(2) ), or AHI, and length of postoperative MV. There was no association between IPFT (C(rs), R(rs), V(T), and FRC) and length of postoperative MV. We conclude that neither PSG nor IPFT can predict the need for prolonged postoperative MV following scoliosis surgery in children who could not reliably perform PFT.

Adolescent↗

Congenital central hypoventilation syndrome: not just another rare disorder.

Congenital central hypoventilation syndrome (CCHS) is a rare syndrome, present from birth, and is defined as the failure of automatic control of breathing. Patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxaemia during sleep and wakefulness. Therefore, especially while asleep, children with CCHS experience progressive hypercapnia and hypoxaemia. They lack arousal responses and sensations of dyspnoea to the endogenous challenges of isolated hypercapnia and hypoxaemia and to the combined stimulus of hypercapnia and hypoxaemia. Patients with CCHS do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis is one of exclusion, ruling out any primary pulmonary, cardiac, metabolic or neurologic cause for central hypoventilation. CCHS is associated with other manifestations of autonomic nervous system dysfunction, including Hirschsprung's disease. All patients with CCHS require lifelong ventilatory support during sleep but some will be able to maintain adequate ventilation without assistance while awake once past infancy. However, some CCHS patients require ventilatory support for 24h/day. Modalities of home mechanical-assisted ventilation include positive pressure ventilation via tracheostomy, non-invasive positive pressure ventilation (bi-level ventilation), negative pressure ventilation and diaphragmatic pacers. Supplemental oxygen alone is inadequate treatment. With early diagnosis and adequate ventilatory support, these children can have good outcomes and lead productive lives.

Child↗

Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach.

The definition of sudden infant death syndrome (SIDS) originally appeared in 1969 and was modified 2 decades later. During the following 15 years, an enormous amount of additional information has emerged, justifying additional refinement of the definition of SIDS to incorporate epidemiologic features, risk factors, pathologic features, and ancillary test findings. An expert panel of pediatric and forensic pathologists and pediatricians considered these issues and developed a new general definition of SIDS for administrative and vital statistics purposes. The new definition was then stratified to facilitate research into sudden infant death. Another category, defined as unclassified sudden infant deaths, was introduced for cases that do not meet the criteria for a diagnosis of SIDS and for which alternative diagnoses of natural or unnatural conditions were equivocal. It is anticipated that these new definitions will be modified in the future to accommodate new understanding of SIDS and sudden infant death.

Humans↗

Long-term pulmonary sequelae in children who were treated with extracorporeal membrane oxygenation for neonatal respiratory failure.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for neonates with intractable respiratory failure, but the long-term pulmonary outcome is unknown. Our aim was to investigate the long-term pulmonary sequelae of these children. STUDY DESIGN: We studied 50 children at 11.1 +/- 1.1 years (mean +/- SD) who had been treated with neonatal ECMO for meconium aspiration syndrome (38%), sepsis (18%), sepsis with pneumonia (12%), congenital diaphragmatic hernia (12%), congenital heart disease (8%), persistent pulmonary hypertension of the newborn (6%), and respiratory distress syndrome (4%) and 27 healthy controls (10.8 +/- 1.6 years). All subjects completed a respiratory questionnaire and performed pulmonary function and graded cardiopulmonary exercise testing. RESULTS: Neonatal ECMO survivors had hyperinflation (median residual volume: 131%), airway obstruction (median forced expired volume in 1 second: 79%), lower oxygen saturation with exercise, and lower peak oxygen consumption than controls. The ECMO group achieved similar exercise minute ventilation to controls, with more rapid and shallow breathing. ECMO survivors had an increased frequency of exercise-induced bronchospasm. Those who required higher inspired oxygen tension and ventilator pressures after weaning from ECMO had lower forced expired volume in 1 second and oxygen saturation values. CONCLUSION: Neonatal ECMO survivors experience lung injury lasting into later childhood. Lung dysfunction correlates with the extent and duration of barotrauma and oxygen exposure as neonates.

Adolescent↗

What are the best pulmonary function test parameters for early detection of post-lung transplant bronchiolitis obliterans syndrome in children?

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is defined as an unexplained fall in forced expiratory volume in 1 s (FEV1) >or=20% of baseline (B). There have been reports in adults that FEF25-75% (>30% decline from B) is more sensitive than FEV1 for the early diagnosis of BOS. Yet, it is not known if other pulmonary function test (PFT) parameters - forced expiratory flow rates at 25-75% of vital capacity (FEF25-75%) and maximal expiratory flow rate at 80% (Vmax80%), 70% (Vmax70%) and 60% (Vmax60%) - are more sensitive indicators for early diagnosis of BOS than FEV1 in post-lung transplant children. We reviewed serial PFTs of 18 patients (ages 14.1 +/- 3.7 yr, 50% female) who had lung transplantation at our institution from 1993 to 1999, and who met the criteria for BOS diagnosis. There was no significant difference in post-transplant days when decline in FEV1 >or=20% of B, FEF25-75% >30% of B, and Vmax80%, Vmax70% and Vmax60% from normal occurred (635 +/- 431, 551 +/- 422 and 454 +/- 287 days, respectively; p = 0.4). However, a decline in FEV1 was the first abnormality in only 39% of the patients, while a decline in FEF25-75% and Vmax at specific lung volume were the first abnormality in 78% and 56% of the patients, respectively. The earliest signs of BOS would be missed in 61% of patients if FEV1 was the primary parameter used for the diagnosis. In order to improve the sensitivity of the diagnosis of post-lung transplant BOS; we speculate that the diagnosis should be based on decreases in FEF25-75% rather than on FEV1.

Adolescent↗

Bordetella bronchiseptica infection in pediatric lung transplant recipients.

Bordetella bronchiseptica are small, pleomorphic Gram-negative coccobacilli which are commensal organisms in the upper respiratory tract of many wild and domestic animals ('kennel cough' in dogs). While it is common for health care providers to ask about exposure to ill family/friends, most do not routinely inquire about the health or immunization status of household pets. We report two cases of B. bronchiseptica pneumonia in lung transplant recipients [cystic fibrosis (CF); ages 10 and 15 yr; one male] who contracted B. bronchiseptica from pet dogs. We compared their course and outcome to four children (two CF, one congenital heart disease and one Duchenne's muscular dystrophy; four males, age range 6 months to 14 yr) with B. bronchiseptica cultured from the respiratory tract. Two of the four patients also acquired their illnesses from pet dogs and two from unknown sources. One lung transplant recipient expired from progressive respiratory failure. We conclude that B. bronchiseptica can cause serious infections in both immunosuppressed and immunocompetent children. We speculate that a detailed history of exposure to ill pets (particularly dogs), and the immunization status of all pets should be included in the routine evaluation of all pediatric transplant recipients.

Adolescent↗

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.

Acute Disease↗

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.

Adult↗