Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group.
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BACKGROUND: Inhaled nitric oxide improves gas exchange in neonates, but the efficacy of low-dose inhaled nitric oxide in reducing the need for extracorporeal membrane oxygenation has not been established. METHODS: We conducted a clinical trial to determine whether low-dose inhaled nitric oxide would reduce the use of extracorporeal membrane oxygenation in neonates with pulmonary hypertension who were born after 34 weeks' gestation, were 4 days old or younger, required assisted ventilation, and had hypoxemic respiratory failure as defined by an oxygenation index of 25 or higher. The neonates who received nitric oxide were treated with 20 ppm for a maximum of 24 hours, followed by 5 ppm for no more than 96 hours. The primary end point of the study was the use of extracorporeal membrane oxygenation. RESULTS: Of 248 neonates enrolled, 126 were randomly assigned to the nitric oxide group and 122 to the control group. Extracorporeal membrane oxygenation was used in 78 neonates in the control group (64 percent) and in 48 neonates in the nitric oxide group (38 percent) (P=0.001). The 30-day mortality rate in the two groups was similar (8 percent in the control group and 7 percent in the nitric oxide group). Chronic lung disease developed less often in neonates treated with nitric oxide than in those in the control group (7 percent vs. 20 percent, P=0.02). The efficacy of nitric oxide was independent of the base-line oxygenation index and the primary pulmonary diagnosis. CONCLUSIONS: Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension. (+info)
Eosinophilic pneumonia and respiratory failure associated with venlafaxine treatment.
(34/1819)
Drugs are well known causes of eosinophilic lung disease. In many patients, symptoms increase slowly, pulmonary infiltrates and eosinophilia progress over weeks, and resolve upon withdrawal of the offending agent. Rarely, the disease presents like acute eosinophilic pneumonia with acute onset of symptoms and rapidly progressing infiltrates which may be associated with respiratory failure. This report describe a case of venlafaxine-induced acute eosinophilic pneumonia causing respiratory insufficiency that rapidly resolved upon institution of corticosteroid treatment. This 5-hydroxytryptamine and noradrenaline reuptake inhibitor was previously not known to cause lung or peripheral blood eosinophilia. Considering the increasing use of this class of medication physicians have to be aware of this life-threatening and fully reversible complication. (+info)
Non-ventilatory treatment of acute hypoxic respiratory failure.
(35/1819)
Severe acute hypoxic respiratory failure is uncommon but often fatal. Standard treatment involves high inspired oxygen concentrations, mechanical ventilation and positive end-expiratory pressure. Many other interventions have been used in parallel with conventional treatment or as rescue therapy when it fails, including extracorporeal gas exchange, prone positioning, inhaled vasodilators, exogenous surfactants and drugs which modify the inflammatory process. Nearly all these treatments improve arterial oxygenation or markers of lung injury. However, the relationship between oxygenation and survival in acute hypoxaemic respiratory failure is not established, so improved oxygenation cannot be used as a surrogate for survival. Randomised controlled trials are, therefore, needed to assess the effects of these treatments on mortality. In such trials, extracorporeal oxygenation and extracorporeal carbon dioxide elimination, surfactant, early methylprednisolone, and prostaglandin E1 offer no survival advantage over conventional therapy. Prophylactic ketoconazole and pentoxifylline appear to improve mortality in small studies in surgical and oncology patients respectively, and methylprednisolone improves mortality and morbidity in unresolving disease. (+info)
Effects of loaded breathing and hypoxia on diaphragm metabolism as measured by (31)P-NMR spectroscopy.
(36/1819)
Diaphragm fatigue may contribute to respiratory failure. (31)P-nuclear magnetic resonance spectroscopy is a useful tool to assess energetic changes within the diaphragm during fatigue, as indicated by P(i) accumulation and phosphocreatine (PCr) depletion. We hypothesized that loaded breathing during hypoxia would lead to diaphragm fatigue and inadequate aerobic metabolism. Seven piglets were anesthetized by using halothane inhalation. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at end expiration with the airway occluded. A nuclear magnetic resonance surface coil placed under the right hemidiaphragm measured P(i) and PCr during four conditions: control, inspiratory resistive breathing (IRB), IRB with hypoxia, and recovery (IRB without hypoxia). IRB alone resulted in hypercarbia (32 +/- 7 to 61 +/- 21 Torr) and respiratory acidosis but no change in diaphragm force output or aerobic metabolism. Combined IRB and hypoxia resulted in decreased force output (Pdi decreased by 40%; from 30 +/- 17 to 19 +/- 11 mmHg) and evidence of metabolic stress (ratio of P(i) to PCr increased by 290%; from 0.19 +/- 0.09 to 0.74 +/- 0.27). We conclude that diaphragm fatigue associated with inadequate aerobic oxidative metabolism occurs in the setting of loaded breathing and hypoxia. Conversely, aerobic metabolism and force output of the diaphragm remain unchanged from control during loaded normoxic or hyperoxic breathing despite the onset of respiratory failure. (+info)
Sleep-related breathing disorders in acute respiratory failure assisted by non-invasive ventilatory treatment: utility of portable polysomnographic system.
(37/1819)
In the majority of patients admitted to an Intensive Care Unit with acute respiratory failure (ARF), the aetiology for ARF is quite evident. In a minority of patients no obvious aetiology is apparent at presentation. In this group a previously unrecognized sleep-related breathing disorder (SRBD) may be the cause of the ARF. In spite of clinical suspicion SRBD remains infrequently diagnosed in ARF also because the technology necessary for this type of diagnosis (polysomnography) is usually unavailable in Intensive Care Units. The aim of this study was to evaluate the utility of portable polysomnography system (PSGp) in a group of patients with ARF of unclear aetiology and with a clinical suspicion of SRBD. We studied a selected group of 14 patients (eight males, six females) admitted to an Intermediate Intensive care unit with varying degree of acute respiratory failure. Mean (SD) age was 57 (13) years, pH 7.28 (0.04), PaO2 5.6 (0.7) kPa), PaO2 (8.8 (1.6) kPa), Body mass index 42.7 (9.6) kg m(-2). The patients had no history of skeletal, neuromuscular or cardiovascular disease. None of them had a history of overt chronic lung diseases or had obvious respiratory tract infections. They were submitted to cardiac and respiratory functional evaluation and to nightly PSGp (VITALOG HMS 5000, Respironics Inc., Redwood City, CA, U.S.A.) which was performed in an intermediate intensive care unit. Ten subjects had obstructive sleep apnoea-hypopnoea syndrome (OSAS), with mean respiratory disorder index h(-1) (RDI) 60.1 (25.9) [in five associated with obesity-hypoventilation syndrome (OHS)]; two had central sleep apnoea with mean RDI 45 (28.3) (one with hypothyroidism and one with cerebral multiple infarctions and right hemidiaphragmatic paralysis) and two had OHS with mean RDI 12.5 (3.5). Nocturnal hypoventilation was present in almost all patients. Continuous positive airway pressure (CPAP) was effective in three patients. Eight patients needed to be treated with BILEVEL (BiPAP, Respironics Inc.) airway positive pressure in timed or spontaneous/timed modes. Two patients required intubation and mechanical ventilatory treatment. In one patient with hypothyroidism was sufficient to institute hormonal therapy. Our study shows that acute respiratory failure due to SRBD is not exceptional in an Intermediate Intensive Care Unit and that if clinical suspicion is strong, portable polysomnography may yield diagnostic confirmation and help in establishing appropriate treatment and in avoiding the invasive ventilatory treatment. (+info)
Expiratory flow limitation as a determinant of orthopnea in acute left heart failure.
(38/1819)
OBJECTIVES: To assess the contribution of expiratory flow limitation (FL) in orthopnea during acute left heart failure (LHF). BACKGROUND: Orthopnea is typical of acute LHF, but its mechanisms are not completely understood. In other settings, such as chronic obstructive pulmonary disease, dyspnea correlates best with expiratory FL and can, therefore, be interpreted as, in part, the result of a hyperinflation-related increased load to the inspiratory muscles. As airway obstruction is common in acute LHF, postural FL could contribute to orthopnea. METHODS: Flow limitation was assessed during quiet breathing by applying a negative pressure at the mouth throughout tidal expiration (negative expiratory pressure [NEP]). Flow limitation was assumed when expiratory flow did not increase during NEP. Twelve patients with acute LHF aged 40-98 years were studied seated and supine and compared with 10 age-matched healthy subjects. RESULTS: Compared with controls, patients had rapid shallow breathing with slightly increased minute ventilation and mean inspiratory flow. Breathing pattern was not influenced by posture. Flow limitation was observed in four patients when seated and in nine patients when supine. In seven cases, FL was induced or aggravated by the supine position. This coincided with orthopnea in six cases. Only one out of the five patients without orthopnea had posture dependent FL. Control subjects did not exhibit FL in either position. CONCLUSIONS: Expiratory FL appears to be common in patients with acute LHF, particularly so when orthopnea is present. Its postural aggravation could contribute to LHF-related orthopnea. (+info)
Neonatal lethality with abnormal neurogenesis in mice deficient in DNA polymerase beta.
(39/1819)
DNA polymerase beta (Polbeta) has been implicated in base excision repair in mammalian cells. However, the physiological significance of this enzyme in the body remains unclear. Here, we demonstrate that mice carrying a targeted disruption of the Polbeta gene showed growth retardation and died of a respiratory failure immediately after the birth. Histological examination of the embryos revealed defective neurogenesis characterized by apoptotic cell death in the developing central and peripheral nervous systems. Extensive cell death occurred in newly generated post-mitotic neuronal cells and was closely associated with the period between onset and cessation of neurogenesis. These findings indicate that Polbeta plays an essential role in neural development. (+info)
Effect of non-invasive mechanical ventilation on sleep and nocturnal ventilation in patients with chronic respiratory failure.
(40/1819)
BACKGROUND: Chronic respiratory failure (CRF) is associated with nocturnal hypoventilation. Due to the interaction of sleep and breathing, sleep quality is reduced during nocturnal hypoventilation. Non-invasive mechanical ventilation (NMV), usually performed overnight, relieves symptoms of hypoventilation and improves daytime blood gas tensions in patients with CRF. The time course of the long term effect of NMV on sleep and breathing during both spontaneous ventilation (withdrawing the intervention) and NMV was investigated in patients with CRF due to thoracic restriction. METHODS: Fifteen consecutive patients (13 women) of mean (SD) age 57.9 (12.0) years with CRF due to thoracic restriction were included in the study. During the one year observation period four polysomnographic studies were performed: three during spontaneous breathing without NMV-before initiation of NMV (T0) and after withdrawing NMV for one night at six months (T6) and 12 months (T12-)-and the fourth during NMV after 12 months (T12+). Daytime blood gas tensions and lung function were also measured. RESULTS: Spontaneous ventilation (in terms of mean oxygen saturation) progressively improved (from T0 to T12-) during both REM sleep (24.8%, 95% CI 12.9 to 36.9) and NREM sleep (21.5%, 95% CI 12.4 to 30.6). Sleep quality during spontaneous ventilation also improved in terms of increased total sleep time (26. 8%, 95% CI 11.6 to 42.0) and sleep efficiency (17.5%, 95% CI 5.4 to 29.6) and decreased awakenings (54.0%, 95% CI 70.3 to 37.7). Accordingly, REM and NREM sleep stages 3 and 4 significantly improved. However, the most significant improvements in both nocturnal ventilation and sleep quality were seen during NMV at 12 months. CONCLUSIONS: After long term NMV both spontaneous ventilation during sleep and sleep quality in patients with CRF due to thoracic restriction showed evidence of progressive improvement compared with baseline after withdrawal of NMV for a single night at six and 12 months. However, the greatest improvements in nocturnal ventilation and sleep were achieved during NMV at 12 months. (+info)