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Anesthesia and Analgesia Feb 2002Shivering is a frequent complication in the postoperative period. The relative efficacy of interventions that are used for the treatment of postoperative shivering is... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Shivering is a frequent complication in the postoperative period. The relative efficacy of interventions that are used for the treatment of postoperative shivering is not well understood. We performed a systematic search (MEDLINE, EMBASE, Cochrane Library, hand searching, all languages, to August, 2000) for full reports of randomized comparisons of any pharmacological antishivering intervention (active) with placebo (control) in the postoperative period. Dichotomous data on absence of further shivering after treatment and adverse effects were extracted from original reports. Relative risk (RR) and number-needed-to-treat (NNT) were calculated with 95% confidence interval (CI) using a fixed effect model. Data from 20 trials (944 adults received an active intervention, 413 were controls) were analyzed. Antishivering efficacy depended on the active regimen and the length of follow-up. Efficacy with meperidine 25 mg, clonidine 150 microg, ketanserin 10 mg, and doxapram 100 mg was reported in at least three trials; all were significantly more effective than control. After 1 min, the NNT of meperidine 25 mg for no further shivering compared with placebo was 2.7 (RR, 6.8; 95% CI, 2.5-18.5). After 5 min, the NNT of meperidine 25 mg was 1.3 (RR, 9.6; 95% CI, 5.7-16), the NNT of clonidine 150 microg was 1.3 (RR, 6.8; 95% CI, 3.3-14.2), the NNT of doxapram 100 mg was 1.7 (RR 4.0; 95% CI, 2.4-6.5), and the NNT of ketanserin 10 mg was 2.3 (RR 3.1; 95% CI, 1.9-5.1). After 10 min, the NNT of meperidine 25 mg was 1.5 (RR 4.0; 95% CI, 2.5-6.2). After 15 min, the NNT of ketanserin 10 mg was 3.3 (RR 1.5; 95% CI, 1.2-1.9). Long-term outcome data were lacking. There were not enough data for alfentanil, fentanyl, morphine, nalbuphine, lidocaine, magnesium, metamizol, methylphenidate, nefopam, pentazocine, and tramadol to draw meaningful conclusions. Reporting of adverse drug reactions was sparse. Fewer than two shivering patients need to be treated with meperidine 25 mg, clonidine 150 microg, or doxapram 100 mg for one to stop shivering within 5 min who would have continued to shiver had they all received a placebo.
IMPLICATIONS
Less than two shivering patients need to be treated with meperidine 25 mg, clonidine 150 microg, or doxapram 100 mg for one to stop shivering within 5 min who would have continued to shiver had they all received a placebo.
Topics: Adrenergic alpha-Agonists; Analgesics, Opioid; Clonidine; Humans; Ketanserin; Lidocaine; Meperidine; Postoperative Complications; Randomized Controlled Trials as Topic; Shivering
PubMed: 11812718
DOI: 10.1097/00000539-200202000-00043 -
The Cochrane Database of Systematic... 2001Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and... (Review)
Review
BACKGROUND
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.
OBJECTIVES
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?
SEARCH STRATEGY
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 '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. Abstracts of the Society for Pediatric Research were searched from 1996 - 2001 inclusive. Also an expert informant's search in the Japanese language was made by Prof. Y. Ogawa in 1996.
SELECTION CRITERIA
All trials utilising random or quasi-random patient allocation, in which doxapram was used for the treatment of apnea in preterm infants were included.
DATA COLLECTION AND ANALYSIS
Each author evaluated the papers for quality and inclusion criteria. Independent data extraction was carried out.
MAIN RESULTS
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.
REVIEWER'S CONCLUSIONS
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.
Topics: Apnea; Doxapram; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Respiratory System Agents
PubMed: 11687067
DOI: 10.1002/14651858.CD000074 -
The Cochrane Database of Systematic... 2000Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and... (Review)
Review
BACKGROUND
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.
OBJECTIVES
To assess the effects of doxapram compared with methylxanthine in preterm infants with recurrent apnea.
SEARCH STRATEGY
The Cochrane Collaboration Clinical Trials Register (Cochrane Library issue 3, 2000), MEDLINE (1966- July 2000), reference lists of relevant articles and conference proceedings.
SELECTION CRITERIA
Randomized and quasi-randomized trials of doxapram compared with methylxanthine (e.g. theophylline, aminophylline or caffeine) for the treatment of apnea in preterm infants.
DATA COLLECTION AND ANALYSIS
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.
MAIN RESULTS
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.
REVIEWER'S CONCLUSIONS
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.
Topics: Aminophylline; Apnea; Doxapram; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Randomized Controlled Trials as Topic; Respiratory System Agents; Theophylline; Xanthines
PubMed: 11034672
DOI: 10.1002/14651858.CD000075 -
The Cochrane Database of Systematic... 2000When preterm infants have been given intermittent positive pressure ventilation (IPPV) for respiratory failure, weaning from support and tracheal extubation may be... (Review)
Review
BACKGROUND
When preterm infants have been given intermittent positive pressure ventilation (IPPV) for respiratory failure, weaning from support and tracheal extubation may be difficult. A significant contributing factor is thought to be the relatively poor respiratory effort and tendency to develop hypoventilation and apnea, particularly in very preterm infants. Doxapram stimulates breathing and appears to act via stimulation of both the peripheral chemoreceptors and the central nervous system. This effect might increase the chance of successful tracheal extubation.
OBJECTIVES
In preterm infants being weaned from IPPV and in whom endotracheal extubation is planned, does treatment with doxapram reduce the use of intubation and IPPV, or reduce other morbidity, without clinically important side effects? In this regard, how does doxapram compare with standard treatment or with an alternative treatment such as methylxanthine or CPAP? Subgroup analyses were prespecified according to birth weight and/or gestational age, use of co-interventions (methylxanthines or nasal CPAP), and route of administration (intravenous or oral).
SEARCH STRATEGY
The standard search strategy of the Neonatal Review Group as outlined in the Cochrane Library was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE and EMBASE.
SELECTION CRITERIA
Eligible studies included published trials utilising random or quasi-random patient allocation in which preterm or low birth weight infants being weaned from IPPV were given doxapram compared with standard care or other treatments, to facilitate weaning from IPPV and endotracheal extubation. Trials were independently assessed by the authors before inclusion.
DATA COLLECTION AND ANALYSIS
The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Each author extracted data separately; the results were compared and any differences resolved. The data were synthesized using the standard method of Neonatal Review Group with use of relative risk and risk difference.
MAIN RESULTS
Two trials involving a total of 85 infants compared doxapram and placebo. In both the individual trials and the meta-analyses there were no significant differences between the doxapram and placebo groups in any of the outcomes (failed extubation, death before discharge, respiratory failure, duration of IPPV, side effects, oxygen at 28 days or oxygen at discharge). There was a trend towards an increase in side effects (hypertension or irritability leading to cessation of treatment) in the doxapram group [summary RR 3.21 (0.53, 19.43). In one of these two trials (Huon 1998) an 'alarming rise in blood pressure' occurred in five infants in the doxapram group and none of the controls, although in only one was treatment withdrawn. One additional trial involving only eight infants compared doxapram with aminophylline, but there were insufficient data for meaningful analysis.
REVIEWER'S CONCLUSIONS
The evidence does not support the routine use of doxapram to assist endotracheal extubation in preterm infants who are eligible for methylxanthine and/or CPAP. The results should be interpreted with caution because the small number of infants studied does not allow reliable assessment of the benefits and harms of doxapram. Further trials are required to evaluate the benefits and harms of doxapram compared with no treatment or with other treatments, such as methylxanthines or CPAP, to evaluate whether it is more effective in infants not responding to these other treatments, and to assess whether the drug is effective when given orally.
Topics: Doxapram; Humans; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Intubation, Intratracheal; Randomized Controlled Trials as Topic; Respiratory System Agents; Ventilator Weaning
PubMed: 10908519
DOI: 10.1002/14651858.CD001966 -
The Cochrane Database of Systematic... 2000COPD is a progressive illness and in the later stages, exacerbations may lead to ventilatory failure. The combination of hypoxia and hypercapnia can lead to coma and... (Review)
Review
BACKGROUND
COPD is a progressive illness and in the later stages, exacerbations may lead to ventilatory failure. The combination of hypoxia and hypercapnia can lead to coma and death. Correction of these blood gas abnormalities is a medical emergency. Doxapram is a respiratory stimulant used to stimulate breathing in this setting.
OBJECTIVES
The objective of this review was to assess the effects of doxapram on gas exchange and clinical outcomes in people with ventilatory failure due to acute exacerbations of chronic obstructive pulmonary disease.
SEARCH STRATEGY
We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted experts in the field, study authors and drug companies.
SELECTION CRITERIA
Randomised trials comparing doxapram with other treatments or placebo in people with ventilatory failure due to exacerbations of chronic obstructive pulmonary disease.
DATA COLLECTION AND ANALYSIS
One reviewer assessed trial quality and extracted data.
MAIN RESULTS
Three trials involving 127 people were included. The trials were of variable quality. Doxapram was marginally superior to placebo in preventing blood gas deterioration (odds ratio 0.38, 95% confidence interval 0.14 to 1.02). In one small study, of 17 patients, doxapram and non-invasive ventilation appeared equally effective in terms of blood gases changes, although there were slightly more deaths with doxapram (odds ratio 11.34, 95% confidence interval 1.00 to 128.03).
REVIEWER'S CONCLUSIONS
Doxapram may improve blood gas exchange in the short term, but newer techniques such as non-invasive ventilation may be more effective.
Topics: Acute Disease; Doxapram; Humans; Lung Diseases, Obstructive; Respiratory Insufficiency; Respiratory System Agents
PubMed: 10796514
DOI: 10.1002/14651858.CD000223 -
The Cochrane Database of Systematic... 2000Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and... (Review)
Review
BACKGROUND
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.
OBJECTIVES
In preterm infants with recurrent apnea, how does treatment with doxapram compare with treatment with theophylline in leading to a clinically important reduction in apnea and use of mechanical ventilation, without clinically important side effects.
SEARCH STRATEGY
The standard search strategy of the Neonatal Review Group, as outlined in the Cochrane Library, was used.
SELECTION CRITERIA
All trials utilising random or quasi-random patient allocation, in which doxapram was compared with methylxanthine (e.g. theophylline) for the treatment of apnea, were eligible. There must have been an effort to exclude specific causes of apnea.
DATA COLLECTION AND ANALYSIS
The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used to select trials, assess quality and to extract and synthesize data. The methodological quality of each trial was reviewed by the second author blinded to trial authors and institution(s). Additional information was requested from authors to clarify methodology. Each author extracted the data separately, then they were compared and differences resolved. Meta-analysis was carried out with use of relative risk and risk difference.
MAIN RESULTS
In these trials involving a relatively small number of preterm infants with apnea of prematurity, there is no apparent difference between the effect of intravenous treatment with doxapram or methylxanthine on the incidence of apnea within 48 hours. There were no infants reported to have been given mechanical ventilation on either treatment. No adverse effects were reported.
REVIEWER'S CONCLUSIONS
Implications for practice. The overall results of these small trials suggest that intravenous doxapram and intravenous methylxanthine are not different in their effectiveness in the short term in the treatment of apnea of prematurity. Caution is warranted as the number of patients in these trials is too small to exclude an important difference between these two treatments or to exclude the possibility of less common side effects. Longer term outcome of infants treated in these trials has not been reported. Implications for research. Further studies would require a large number of infants, stratified by gestation, to clarify which infants are likely to benefit and whether there might be differences in responses or side effects with these two drugs at different ages. It would be valuable to include important clinical outcomes such as use of mechanical ventilation as well as subsequent growth and development in future studies. Responses to treatment would have to take account of co-interventions, such as nasal continuous airway pressure which is frequently used post-intubation.
Topics: Aminophylline; Apnea; Doxapram; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Respiratory System Agents; Theophylline; Xanthines
PubMed: 10796115
DOI: 10.1002/14651858.CD000075 -
The Cochrane Database of Systematic... 2000Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and... (Review)
Review
BACKGROUND
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.
OBJECTIVES
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?
SEARCH STRATEGY
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.
SELECTION CRITERIA
All trials utilising random or quasi-random patient allocation, in which doxapram was used for the treatment of apnea in preterm infants were included.
DATA COLLECTION AND ANALYSIS
Each author evaluated the papers for quality and inclusion criteria. Independent data extraction was carried out.
MAIN RESULTS
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.
REVIEWER'S CONCLUSIONS
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.
Topics: Apnea; Doxapram; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Respiratory System Agents
PubMed: 10796114
DOI: 10.1002/14651858.CD000074