Loss Of Breathing Research Articles

Kinesthetic stimulation for preventing apnea in preterm infants.

Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia, which may be severe enough to require resuscitation including use of positive pressure ventilation or other treatments. Physical stimulation is often used to restart breathing and it is possible that repeated stimulation, such as with an oscillating mattress (kinesthetic stimulation), might prevent apnea and its consequences. In preterm infants at risk for apnea, does prophylactic use of kinesthetic stimulation lead to a clinically important reduction in apnea and bradycardia, and use of intemittent positive preswsure ventilation (IPPV). The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. All trials in preterm infants at risk of developing clinical apnea which utilised random or quasi-random allocation to treatment with an oscillating mattress or control, were eligible. Standard methods of the Cochrane Collaboration and its Neonatal Review Group were used with separate evaluation of trial quality and data extraction by each author and synthesis of the data using relative risk. There were no differences in short term effects (apnea /bradycardia, IVH, use of IPPV, sleep/wake cycles and neurological status at discharge) or longterm effects (in one trial - growth and development to one year). Implications for practice. Prophylactic use of kinesthetic stimulation cannot be recommended to reduce apnea/bradycardia in preterm infants. Implications for research. There are currently no clear research questions regarding prophylactic use of kinesthetic stimulation to prevent apnea in preterm infants.

Doxapram treatment for apnea in preterm infants.

Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Doxapram has been used to stimulate breathing and so prevent apnea and its consequences. In preterm infants with recurrent apnea, does treatment with doxapram lead to a clinically important reduction in apnea and use of Intermittent positive airways pressure (IPPV), without clinically important side effects? Searches were made of the Oxford Database of Perinatal trials, the Cochrane Collaboration Clinical Trials Register, MEDLINE (using text words 'doxapram', 'apnea or apnoea' and Mesh term 'infant, premature') previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, mainly in the English language. Also an expert informant's search in the Japanese language was made by Prof. Y. Ogawa in 1996. All trials utilising random or quasi-random patient allocation, in which doxapram was used for the treatment of apnea in preterm infants were included. Each author evaluated the papers for quality and inclusion criteria. Independent data extraction was carried out. Only one trial, which randomized 11 infants to intravenous doxapram and 10 infants to placebo, was found. There were fewer treatment failures after 48 hours in the group of preterm infants treated with doxapram (4/11) compared with the group treated with placebo (8/10). The wide confidence intervals made this result non-significant [RR 0.45 (0.20, 1.05)]. Only one infant, who was from the placebo group, was given IPPV. Of the seven responders by 48 hours in the group of 11 who received doxapram, five failed to respond between 48 hours and seven days after commencement of therapy. This gives a late failure rate of 9/11, similar to the short term failure rate in the placebo group of 8/10. It is not possible to evaluate the late responses of all those in the placebo group since they crossed over to a treatment arm. Although intravenous doxapram might reduce apnea within the first 48 hours of treatment, there are insufficient data to evaluate the precision of this result or to assess potential adverse effects. No longterm outcomes have been measured. Further studies are needed to determine the role of this treatment in clinical practice.

Continuous positive airway pressure versus theophylline for apnea in preterm infants.

Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Theophylline and continuous positive airways pressure (CPAP) are two treatments that have have been used to prevent apnea and its consequences. The main objective was to determine in preterm infants with recurrent apnea, if treatment with CPAP compared with treatment with theophylline leads to a clinically important reduction in apnea or use of mechanical ventilation, without clinically important side effects. Searches were made of the Oxford Database of Perinatal trials, the Cochrane Collaboration Clinical Trials Register, MEDLINE 1966 - July 2001, EMBASE 1980 - July 2001, CINAHL 1982 - July 2001(using text words 'theophylline', 'caffeine', 'CPAP', 'CDAP', 'positive pressure', 'apnea or apnoea' and MeSH term 'infant, premature'), previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, mainly in the English language. Abstracts of the Society for Pediatric Research were searched from 1996 - 2001 inclusive. All trials using random or quasi-random allocation to CPAP or theophylline in preterm infants with clinical recurrent apnea/bradycardia were eligible. Data were extracted using standard methods of the Cochrane Collaboration and its Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk. Only one eligible trial was found. The use of mask CPAP is associated with a higher treatment failure rate as measured by less than a 50% reduction in apnea or use of an alternative treatment [RR 2.89 (95% CI 1.12, 7.47); RD 0.42 (95% CI 0.11, 0.74)]. For every 2.4 infants (95% CI 1.4, 9.5) treated with mask CPAP rather than theophylline, there results one treatment failure. In the mask CPAP group there is more use of IPPV [RR 3.09 (1.42, 6.70); RD 0.58 (95% CI 0.30, 0.86). For every 1.7 infants (95% CI 1.2, 3.3) treated with mask CPAP rather than theophylline, one infant is intubated for IPPV. In the mask CPAP group, there are trends towards more deaths in the first year, and in death or major disability in survivors at follow up, which do not reach significance. There are no differences in rates of necrotizing enterocolitis or major disability in survivors at follow up. Theophylline is more effective than mask CPAP for preterm infants with apnea. Since CPAP is no longer administered by mask, the results of this review have limited importance for current clinical practice. Further evaluation of the benefits and harms of CPAP vs theophylline for preterm infants with apnea requires further trials in which CPAP is administered by current methods.

Methylxanthine treatment for apnea in preterm infants.

Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Methylxanthines have been used to stimulate breathing and prevent apnea and its consequences. The objective of this review is to determine if methylxanthine treatment in preterm infants with recurrent apnea leads to a clinically important reduction in apnea and use of intermittent positive pressure ventilation (IPPV), without clinically important side effects. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. All trials utilising random or quasi-random patient allocation, in which methylxanthine (theophylline or caffeine) was compared with placebo or no treatment for apnea in preterm infants, were included. Methodological quality was assessed independently by the two authors. Data were extracted independently by the two authors. Treatment effects were expressed as relative risk (RR) and risk difference (RD) and their 95% confidence intervals, using a fixed effect model. For significant results, the inverse of the risk difference (1/RD) was used to calculate the number needed to treat (NNT). The results of four trials which enrolled a total of 110 preterm infants with apnea indicate that methylxanthine therapy leads to a reduction in apnea and use of IPPV in the first 2 - 7 days. There are insufficient data to evaluate side effects and no data to examine effects within different gestational age groups. There are no trial data which examine long term effects. Methylxanthines are effective in reducing the number of apneic attacks and the use of mechanical ventilation in the two to seven days after starting treatment. In view of its lower toxicity, caffeine would be the preferred drug. Although the safety of methylxanthine therapy has been suggested in cohort studies, there are no trial data on longterm outcome. In order to indicate which infants are likely to benefit from treatment, there is a need for stratification by gestation and/or other risk factors in future studies. In any future studies the longer term effects of treatment on growth and development should be evaluated.

Doxapram versus methylxanthine for apnea in preterm infants.

Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Doxapram and methylxanthine drugs have been used to stimulate breathing and so prevent apnea and its consequences. To assess the effects of doxapram compared with methylxanthine in preterm infants with recurrent apnea. The Cochrane Collaboration Clinical Trials Register (Cochrane Library issue 3, 2000), MEDLINE (1966- July 2000), reference lists of relevant articles and conference proceedings. Randomized and quasi-randomized trials of doxapram compared with methylxanthine (e.g. theophylline, aminophylline or caffeine) for the treatment of apnea in preterm infants. The methodological quality of each trial was reviewed by the second reviewer blinded to trial authors and institution(s). Additional information was requested from authors. Each reviewer extracted the data separately, then they were compared and differences resolved. Meta-analysis was carried out with use of relative risk and risk difference. Three trials involving 56 infants were included. No difference was detected between intravenous doxapram or methylxanthine in the incidence of failed treatment within 48 hours (relative risk 1.16, 95% confidence interval 0.43 to 3.13). No infants were reported to have been given mechanical ventilation on either treatment. No adverse effects were reported. Intravenous doxapram and intravenous methylxanthine appear to be similar in their short term effects for treating apnea in preterm infants, although these trials are too small to exclude an important difference between the two treatments or to exclude the possibility of less common adverse effects. Longer term outcome of infants treated in these trials has not been reported. Further studies would require a large number of infants to clarify whether there might be differences in responses or adverse effects with these two drugs at different ages.

Nasal respiratory turbinate function in birds.

Nasal respiratory turbinates are complex, epithelially lined structures in nearly all birds and mammals that act as intermittent countercurrent heat exchangers during routine lung ventilation. This study examined avian respiratory turbinate function in five large bird species (115-1,900 g) inhabiting mesic temperate climates. Evaporative water loss and oxygen consumption rates of birds breathing normally (nasopharyngeal breathing) and with nasal turbinates experimentally bypassed (oropharyngeal breathing) were measured. Water and heat loss rates were calculated from lung tidal volumes and nasal and oropharyngeal exhaled air temperatures (T(ex)). Resulting data indicate that respiratory turbinates are equally adaptive across a range of avian orders, regardless of environment, by conserving significant fractions of the daily water and heat budget. Nasal T(ex) of birds was compared to that of lizards, which lack respiratory turbinates. The comparatively high nasal T(ex) of the lizards in similar ambient conditions suggests that their relatively low metabolic rates and correspondingly reduced lung ventilation rates may have constrained selection on similar respiratory adaptations.

Prophylactic methylxanthine for preventing of apnea in preterm infants.

Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. In infants with apnea, methylxanthines have been successful as treatment to prevent further episodes. It is possible that prophylactic therapy, given to all very preterm infants from soon after birth, might prevent apnea and its associated hypoxemia and bradycardia. In preterm infants, does prophylactic treatment with methylxanthine lead to less apnea, bradycardia, episodes of hypoxemia and use of mechanical ventilation, without clinically important side effects? The standard strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants and journal handsearching mainly in the English language. A search of MEDLINE was made in October 1998 covering the years 1966 -1998. All trials utilising random or quasi-random patient allocation, in which prophylactic methylxanthine (caffeine or theophylline) was compared with placebo or no treatment were eligible. Outcomes sought included the rate of apnea, bradycardia, hypoxemic episodes, use of IPPV, side effects such as tachycardia or feed intolerance, as well as longer term abnormal growth and development. The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The methodological quality of each trial was reviewed independently by each author. Each reviewer extracted data separately, then results were compared and differences resolved. The standard method of the Cochrane Neonatal Review Group was used to analyze the data, utilizing relative risk (RR) and risk difference (RD). Two studies examining a total of 104 infants were found. Both studied the effects of prophylactic caffeine. There were no meaningful differences between the caffeine and placebo groups in the number of infants with apnea, bradycardia, hypoxemic episodes, use of IPPV or side effects in either of the studies. Only two outcomes (use of IPPV and tachycardia) were common to the two studies and meta-analysis showed no substantive differences between the groups. The results of this review do not support the use of prophylactic caffeine for preterm infants at risk of apnea, bradycardia or hypoxemic episodes. Any future studies need to examine the effects of prophylactic methylxanthines in preterm infants at higher risk of apnea, bradycardia or hypoxemic episodes. This should include examination of important clinical outcomes such as need for IPPV, length of hospital stay and long term development.

Caffeine versus theophylline for apnea in preterm infants.

Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Two forms of methylxanthine (caffeine and theophylline) have been used to stimulate breathing and so prevent apnea and its consequences. In preterm infants with recurrent apnea, does caffeine treatment compared to theophylline treatment lead to a clinically important reduction in apnea and use of mechanical ventilation without clinically important side effects? Standard strategies of the Neonatal Review Group were used. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE (see main text for strategy), previous reviews including cross references, abstracts conferences and symposium proceedings, expert informants, journal handsearching mainly in the English language. Also an expert informant's search in the Japanese language was made by Prof Y. Ogawa. All trials utilising random or quasi-random patient allocation in which caffeine was compared with theophylline for the treatment of apnea were eligible. Trial quality and eligibility were assessed independently by each author. There must have been an effort to exclude specific causes of apnea. Measures of the severity of apnea as well as the response to treatment must have been consistent with an evaluation of 'clinical apnea' as defined by the American Academy of Pediatrics (Nelson 1978). Standard method of Neonatal Review Group was used. Each author assessed eligibility, trial quality and extracted data separately, then compared and resolved differences. Results are expressed as relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) was calculated. There is no difference in the failure rate (< 50% reduction in apnea/bradycardia) of treatment with caffeine or theophylline at 1-3 (two studies) or 5-7 days (one study). There is a higher mean rate of apnea in the standard caffeine group at 1-3 days [three studies, mean diff. 0.398 (0.334,0.463) /100min] but not at 5-7 days (two studies). Side effects, as indicated by tachycardia or feed intolerance leading to change in dosing, are lower in the caffeine group [typical RR 0.17 (0.04,0.72), RD -0.285 (-0.467,-0.104), NNT 3.5 (2.1, 9.6)]. This was consistent across the three studies. No trial reported the use of IPPV and no data are available to assess effects on growth and development. Caffeine appears to have similar short term effects on apnea/bradycardia to theophylline. In view of the other therapeutic advantages of caffeine (a higher therapeutic ratio, more reliable enteral absorption and a longer half life) this is the preferred treatment for apnea in preterm infants. The possibility that higher doses of caffeine might be more effective in extremely preterm infants needs further evaluation in randomized clinical trials.

O-4-51 - Treatment of arteriovenous malformations (AVM) with linac stereotactic radiosurgery: A comparative study with large AVM

Ondine׳s curse is a rare, potentially life-threatening disorder characterized by loss of automatic breathing during sleep and preserved voluntary breathing. It is seldom encountered in the radiotherapy clinic but can pose significant technical challenges and safety concerns in the delivery of a prescribed radiation course. We report a unique case of successful delivery of radiotherapy for ependymoma in a patient with Ondine׳s curse. A 53-year-old gentleman presented with vertigo when lying down. Brain magnetic resonance imaging revealed an enhancing mass in the floor of the fourth ventricle. He underwent maximal safe resection. Pathology revealed ependymoma. The patient was referred for radiotherapy. Computed tomography simulation was performed in supine position with 3-point thermoplastic mask immobilization. Sequential TomoTherapy plans were developed. At first scheduled treatment, shortly after mask placement, his arms went limp and he was unresponsive. Vitals showed oxygen saturation 83%, pulse 127, and blood pressure 172/97 mm Hg. He was diagnosed with Ondine׳s curse thought secondary to previous brainstem damage; the combination of lying flat and pressure from the mask was causing him to go into respiratory arrest. As supine positioning did not seem clinically advisable, he was simulated in prone position. A RapidArc plan and a back-up conformal plan were developed. Prescriptions were modified to meet conservative organs-at-risk constraints. Several strategies were used to minimize uncertainties in set-up reproducibility associated with prone positioning. He tolerated prone RapidArc treatments well. The report highlights the importance of applying practical patient safety and treatment planning/delivery strategies in the management of this challenging case.

Relationship between fetal biophysical activities and umbilical cord blood gas values

In a prospective study of 62 patients undergoing cesarean section before the onset of labor a fetal biophysical profile assessment was performed within 3 hours before the cesarean section. The presence or absence of the individual fetal biophysical activities (fetal heart rate reactivity, fetal breathing movements, fetal body movements, and fetal tone) were correlated with umbilical cord blood gas and acid-base measurements (artery and vein). Fetuses with nonreactive nonstress test results or the absence of breathing had significantly lower cord artery pH 1 P0 2 bicarbonate, and base excess measurements but not a significantly different PC0 2 level as compared with fetuses that had these activities present. Fetuses with the absence of movements or tone had lower pH 1 P0 2 bicarbonate, and base excess levels and higher PC0 2 levels as compared with fetuses with the presence of movements or tone, respectively. These blood gas and acid-base differences were observed in both umbilical cord artery and vein. Subsequent analysis of the blood gas and acid-base measurements of the fetuses with compromised biophysical activities revealed that there are different levels of acidemia, hypoxemia, and hypercapnia at which the individual biophysical activities are compromised. These data suggest that the first manifestations of fetal hypoxemia and acidemia are nonreactive nonstress test results and loss of fetal breathing; in advanced acidemia, hypoxemia, and hypercapnia fetal movements and fetal tone are compromised.

The relationships among the fetal biophysical profile, umbilical cord pH, and Apgar scores

The relationships among the fetal biophysical profile, umbilical cord blood pH, and Apgar scores were investigated in 124 patients undergoing cesarean section before the onset of labor. Based on a standard for the diagnosis of fetal acidosis of an umbilical cord arterial pH less than 7.20, the sensitivity, specificity, and positive and negative predictive values of the fetal biophysical profile score were 90%, 96%, 82%, and 98%, respectively. When the combination of a nonreactive nonstress test and absent fetal breathing was used as the "abnormal test," the sensitivity, specificity, and positive and negative predictive values were 100%, 92%, 71%, and 100%, respectively. The efficacy of the fetal biophysical profile to indicate fetal acidosis was found to be superior to the 1- and 5-minute Apgar scores in sensitivity and positive predictive value. These data suggest that the biophysical profile is very accurate in the identification of the fetus with acidemia. The first manifestations of fetal acidosis are nonreactive nonstress testing and loss of fetal breathing; in advanced acidemia fetal movements and fetal tone are compromised. A new protocol of antepartum fetal evaluation is suggested based on individual biophysical components rather than the score alone.