Rhabdomyolysis due to rosuvastatin in a patient with ROHHAD syndrome.

We report a 13-year-old female with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome, panhypopituitarism, dyslipidemia, type 2 diabetes mellitus, and nonalcoholic fatty liver disease, who developed rhabdomyolysis and acute kidney injury, two weeks after switching from lovastatin to rosuvastatin. She had been on lovastatin for eight years without any adverse effects.

Carbamazepine Improves Apneic Episodes in Congenital Central Hypoventilation Syndrome (CCHS) With a Novel PHOX2B Exon 1 Missense Mutation.

ABSTRACT: Pathogenic variants in Paired-Like Homeobox 2B (PHOX2B) gene cause congenital central hypoventilation syndrome (CCHS), a rare disorder of the nervous system characterized by absent or reduced ventilatory response to hypoxia and hypercapnia. The focus of management in CCHS is optimizing ventilation. Thus far, no medication has proved effective in improving ventilation. Most CCHS cases are caused by polyalanine repeat expansion mutations. Non-polyalanine repeat expansion mutations are the cause in 8% of cases and result in a more severe clinical presentation. PHOX2B has 3 exons. Exon 3 of PHOX2B is the most common location for CCHS-causing mutations. Thus far, only 9 CCHS-causing mutations have been reported in exon 1, 8 of which were nonsense mutations. We report a child with CCHS who was found to have a novel heterozygous missense variant in exon 1; c.95A > T. Improvement in his apneic episodes was observed following treatment with carbamazepine.

Intravenous Caffeine Rescue for Postoperative Hypoventilation in a 16-Year-Old With Trisomy 10: A Case Report.

Trisomy 10 is a rare disorder, with only 35 cases reported in the literature. Anesthetic management may be challenging in this patient population because of craniofacial, cardiac, and renal abnormalities commonly seen in the disorder. We describe a 16-year-old male with an anesthetic history notable for prolonged emergence, postoperative hypoxia, postoperative reintubation, and unexpected hospital admission presenting for dental extraction of impacted teeth. We utilized intravenous caffeine, a respiratory stimulant used in preterm infants, to facilitate recovery from anesthesia.

Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation.

Desogestrel enhances ventilation in ondine patients: Animal data involving serotoninergic systems.

Congenital central hypoventilation syndrome (CCHS) is a neurorespiratory disease characterized by life-threatening sleep-related hypoventilation involving an alteration of CO2/H(+) chemosensitivity. Incidental findings have suggested that desogestrel may allow recovery of the ventilatory response to CO2. The effects of desogestrel on resting ventilation have not been reported. This study was designed to test the hypothesis that desogestrel strengthens baseline ventilation by analyzing the ventilation of CCHS patients. Rodent models were used in order to determine the mechanisms involved. Ventilation in CCHS patients was measured with a pneumotachometer. In mice, ventilatory neural activity was recorded from ex vivo medullary-spinal cord preparations, ventilation was measured by plethysmography and c-fos expression was studied in medullary respiratory nuclei. Desogestrel increased baseline respiratory frequency of CCHS patients leading to a decrease in their PETCO2. In medullary spinal-cord preparations or in vivo mice, the metabolite of desogestrel, etonogestrel, induced an increase in respiratory frequency that necessitated the functioning of serotoninergic systems, and modulated GABAA and NMDA ventilatory regulations. c-FOS analysis showed the involvement of medullary respiratory groups of cell including serotoninergic neurons of the raphe pallidus and raphe obscurus nuclei that seem to play a key role. Thus, desogestrel may improve resting ventilation in CCHS patients by a stimulant effect on baseline respiratory frequency. Our data open up clinical perspectives based on the combination of this progestin with serotoninergic drugs to enhance ventilation in CCHS patients.

Effect of transpleural perfusion with oxygenated perfluorocarbon in a rat model of acute lung injury.

BACKGROUND: Despite advances in critical care, more effective methods of systemic oxygenation in patients with acute lung injury or acute respiratory distress syndrome are needed. The goal of this study was to determine if it is possible to increase systemic oxygenation by transpleural perfusion with oxygenated perfluorocarbon in animals with induced acute lung injury. METHODS: Eighteen Sprague-Dawley rats were intubated, and acute lung injury was induced by aspiration of 0.1N HCl (1 mL/kg) through the tracheal tube. Inflow and outflow tubes were placed in the thoracic cavity and connected to a perfusion circuit containing a roller pump, warmer, and oxygenator. Rats in group I were not treated after aspiration of HCl, those in group II were perfused with oxygenated saline, and those in group III were perfused with oxygenated perfluorocarbon. Arterial blood gases were collected every 30 minutes for 180 minutes. At the last step of the experiments, pathological examination of the lungs and parietal pleura was performed. RESULTS: PaO(2) in group III was significantly higher than that in group I or II. PaCO(2) in group III was significantly lower than that in the other two groups. Histological examination showed relatively well-delineated zones of inflammation-free coagulative necrosis of lung parenchyma in all groups. CONCLUSIONS: Transpleural perfusion with oxygenated perfluorocarbon in an animal model of induced acute lung injury resulted in a significant increase in systemic oxygenation and depletion of systemic carbon dioxide, and might be a useful method for improving systemic oxygenation in patients with acute lung injury.

Congenital central hypoventilation syndrome and desogestrel: a call for caution: addendum to "C. Straus, H. Trang, M.H. Becquemin, P. Touraine, T. Similowski, Chemosensitivity recovery in Ondine's curse syndrome under treatment with desogestrel" [Respir. Physiol. Neurobiol. 171 (2010) 171-174].

Patients suffering from congenital central hypoventilation syndrome (CCHS) depend on mechanical ventilation during sleep, from birth and throughout life. They lack CO2-chemosensitivity. Hope has recently been raised by serendipitous observations of chemosensitivity recovery under treatment by desogestrel, a very potent progestin (Straus et al., 2010). Caution is however needed, because this effect could depend on dose, idiosyncrasies, or be transient. Desogestrel should not be prescribed to CCHS patients with a respiratory purpose until the results of a pending clinical trial (clinicaltrials.gov. NCT01243697) are available.

Benzodiazepines in the acute management of seizures with autonomic manifestations: anticipate complications!

The use of rescue benzodiazepines in the management of seizures is widely accepted in emergency pediatric practice. They can, however, cause severe side effects, such as respiratory depression. We describe five patients who presented with severe respiratory depression following benzodiazepine administration for seizures with autonomic manifestations. We also discuss the relationship between the complications observed in our patients and the rescue treatment. A reduction in the dosage of benzodiazepines in the setting of epileptic patients with predominant autonomic symptoms may need to be considered.

Effects of long-term captopril and L-arginine treatment on ventilation and blood pressure in obese male SHHF rats.

We investigated the effects of captopril (Cap) and L-arginine (Arg) on hypertension and cardiopulmonary function. Our hypothesis was that Cap therapy or Arg will improve cardiopulmonary risk factors for hypertension and hypoventilation in the obese spontaneously hypertensive heart failure rat, which is characterized by hypertension, obesity, and disorders of lipid and carbohydrate metabolism. For the first study, one group of rats received Cap in drinking water, and a second group received deionized water (DI). For the second study, rats were further subdivided. Some Cap-treated rats continued on this treatment, and the other half were now given DI to determine whether there would be residual effects of Cap treatment. A subgroup of rats who had received DI was then given Arg, whereas the rest remained on DI. In the first study, Cap-treated rats exhibited decreases in systolic and diastolic blood pressures, frequency of breathing, and minute ventilation, but ventilatory control was maintained. In contrast, blood pressures and relative ventilation to metabolism were higher in the DI-treated group. Removal of Cap increased blood pressure and decreased tidal volume while these rats maintained frequency. Although Arg-treated rats did not exhibit a decrease of blood pressure, ventilation was maintained in this group by preserving tidal volume. Thus Cap and Arg affected ventilation through different mechanisms independent of blood pressure.

Use of heliox in patients with severe exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To assess whether patients with chronic obstructive pulmonary disease treated with heliox have a better prognosis than those treated with standard therapy. DESIGN: Retrospective analysis over 18 months. SETTING: Academic emergency department. PATIENTS: Eighty-one patients admitted with exacerbation of chronic obstructive pulmonary disease and respiratory acidosis. INTERVENTIONS: Use of helium-oxygen mixture as an adjunctive therapy. MEASUREMENTS AND MAIN RESULTS: The following data were collected: age, gender, medical history, vital signs, arterial blood gas at admission, emergency room treatment, requirement for intubation, admission in intensive care unit, length of stay, and evolution. Patients were classified into two groups according to whether heliox was used as a therapeutic agent (heliox group) or not (standard group). Chi-square test and Student's t-test were used for statistical analysis (significant at p <.05). In both groups, the following data were similar: age, gender, medical history, vital signs, initial arterial blood gas, and emergency room treatment. Significant decreases in intubation, and mortality rate were identified in the heliox group. Significant decreases in intensive care unit stay and in-hospital stay were observed for survivors in the heliox group. CONCLUSION: Use of heliox seems to improve prognosis in patients with severe acute exacerbation of chronic obstructive pulmonary disease. Prospective randomized studies are needed to confirm these results.

Growth hormone treatment of patients with Prader-Willi syndrome. Swedish Growth Hormone Advisory Group.

Several studies have now been published on the effect of one or several years of growth hormone treatment on growth and body composition of children with Prader-Willi syndrome. The majority of the patients have responded with greatly increased growth rate, decreased body fat and increased muscle volume. Many of these children seem to have a functional growth hormone deficiency, probably secondary to their hypothalamic dysfunction. Further studies are needed to establish the long-term effect of this treatment on somatic and psychological well-being.

Pharmacologic treatment of sleep-disordered breathing.

Available literature on the use of pharmacologic agents for the treatment of sleep-disordered breathing was reviewed by evidenced-based methodology. Evidence tables were created and studies were graded according to study design and the number of subjects included. Scores for each group of studies evaluating each pharmacologic agent were established so that the quality of research for different drugs could be compared. The use of various ventilatory stimulants, psychotropic drugs, and antihypertensive agents were reviewed. The most objective data are available on theophylline and opioid antagonist/nicotine groups. Although more controlled studies would be helpful, relatively clear-cut indications for the use of ventilatory stimulants exist for hypercapnic obesity-hypoventilation patients (medroxyprogesterone), myxedema (thyroid replacement), central apnea (acetazolamide), and periodic breathing in congestive heart failure (theophylline). Few randomized, well-controlled trials have been published that evaluate pharmacologic agents in the treatment of classic OSA. To date, no one agent stands out as being useful for OSA. Future research will need to characterize subjects so that various subsets of patients can be tried on one or on a combination of various pharmacologic agents.

GABA(B) receptor blockade reduces resistive loading-induced hypoventilation in anesthetized rabbits.

We hypothesized that hypoventilation induced by resistive loaded breathing may result in part from the inhibition of central respiratory-related structures by gamma-aminobutyric acid (GABA), through the stimulation of GABA(B) receptors. In that case, ventilatory depression should be minimized by GABA(B) receptor blockade. To test this assumption, the ventilatory effects of a GABA(B) receptor antagonist (CGP 35348) were evaluated in two groups of urethane anesthetized rabbits, breathing either through an inspiratory resistive load (IRL group) or not (Control group). CGP 35348 did not modify baseline ventilation in the Control group. On the other hand, it partially reversed IRL-induced hypoventilation through a higher respiratory rate and central inspiratory drive. These data suggest that, unlike GABA(A) receptors, GABA(B) receptors would not play a part in eupneic breathing, but that they could participate in the hypoventilation resulting from an acute increase in the work of breathing.

[The effect of drugs taken by patients with respiratory pathology on the nature of sleep and on respiratory characteristics]. / Effet des drogues prises par les patients présentant une pathologie respiratoire sur l'organisation du sommeil et les caractéristiques respiratoires.

The influence of medications and the usual taken by patients with respiratory disease on the characteristics of sleep and nocturnal respiration is complex, due to the fact of the inter-dependence which exists between these two physiological domains. Numerous medications have been evaluated for the treatment of nocturnal respiratory anomalies observed in patients suffering from chronic airflow obstruction or from a sleep apnoea or hypopnoea syndrome. For the greater part, the efficacy of these drugs remains limited and in the case of nocturnal sleep apnoea no pharmacological approach has an efficacy comparable either to mechanical or surgical treatments. It is thus important in these patients to appreciate the limits of medications prescribed for a specific purpose and the deleterious effect which may occur with certain medications employed for a symptomatic goal.

Short-term use of fluoxetine in asymptomatic obese subjects with sleep-related hypoventilation.

Disordered nocturnal breathing with significant arterial oxygen desaturation and sleep apnoea is a feature of extreme obesity which is often difficult to manage in the short term. We have evaluated the effect of fluoxetine, a centrally acting 5-HT re-uptake inhibitor, on sleep-breathing patterns in asymptomatic extremely obese subjects. A double-blind cross-over study was used to compare fluoxetine (60 mg for three days) to placebo. Eleven obese subjects (ten males, one female, mean weight +/- s.d. 131 +/- 2 kg) slept overnight in a sleep laboratory with the polysomnographic study recorded after an initial acclimatization night. The obese subjects had normal respiratory function and normal fully awake arterial oxygen saturation (%SaO2 97 +/- 1). Marked O2 desaturation was seen in all the subjects during sleep but the average asleep %SaO2 did not differ between the two treatment phases (placebo 90 +/- 5; fluoxetine 92 + 2%). However, fluoxetine significantly increased the minimum %SaO2 recorded during the study night either by abolishing or reducing REM sleep (placebo 73 +/- 2%; fluoxetine 81 +/- 8%; P < 0.05, 95% CI -12.3 to -2.03). Frequent hypopnoea was observed in all subjects in both REM and non-REM sleep whereas apnoea was uncommon. The total apnoea/hypopnoea index fell in six subjects during the fluoxetine night, the largest reduction being seen in the most severely affected. In five of the six the improvement was associated with the abolition of REM sleep. Total sleep time did not differ between the placebo and fluoxetine nights nor did a qualitative assessment of sleep using a visual analogue score.(ABSTRACT TRUNCATED AT 250 WORDS)