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The Cochrane Database of Systematic... 2003COPD 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... (Meta-Analysis)
Meta-Analysis 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 respiration 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. Following electronic searches conducted in November 2001 one further unpublished study has been included in the review.
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
Four trials involving 176 people were included. The trials were of variable quality. Doxapram was marginally superior to placebo in preventing blood gas deterioration. In the two studies comparing doxapram and non-invasive ventilation the results were conflicting: an early small study suggested non-invasive ventilation was superior. However, a subsequent larger study in severe participants suggested doxapram was equally effective in terms of blood gases changes, with no differences observed in mortality and frequent treatment failure.
REVIEWER'S CONCLUSIONS
Doxapram can improve blood gas exchange over the first few hours of treatment. Newer techniques such as non-invasive ventilation may prove to be more effective, although there is no randomised trial evidence to this effect.
Topics: Acute Disease; Doxapram; Humans; Lung Diseases, Obstructive; Randomized Controlled Trials as Topic; Respiratory Insufficiency; Respiratory System Agents
PubMed: 12535393
DOI: 10.1002/14651858.CD000223 -
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 -
Animals : An Open Access Journal From... Mar 2020Anaesthetic drugs are commonly used during the evaluation of laryngeal function in dogs. The aim of this review was to systematically analyse the literature describing... (Review)
Review
Anaesthetic drugs are commonly used during the evaluation of laryngeal function in dogs. The aim of this review was to systematically analyse the literature describing the effects of anaesthetic drugs and doxapram on laryngeal motion in dogs and to determine which drug regime provides the best conditions for laryngeal examination. PubMed, Google Scholar, and EMBASE databases were used for the literature search up to November 2019. Relevant search terms included laryngeal motion, anaesthetic drugs and dogs. Studies were scored based on their level of evidence (LoE), according to the Oxford Centre for Evidence-based Medicine, and the quality was assessed using the risk-of-bias tool and SIGN-checklist. In healthy dogs, premedication before laryngeal examination provided better examination conditions and maintained overall adequate laryngeal motion in 83% of the studies. No difference in laryngeal motion between induction drugs was found in 73% of the studies but the effects in dogs with laryngeal paralysis remain largely unknown. Doxapram increased laryngeal motion in healthy dogs without serious side effects, but intubation was necessary for some dogs with laryngeal paralysis. Methodological characteristics varied considerably between studies, including the technique and timing of evaluation, number of assessors, study design, drug dose, combinations, route and speed of administration.
PubMed: 32235700
DOI: 10.3390/ani10030530 -
The Cochrane Database of Systematic... Apr 2006The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during sleep. However this is not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during sleep. However this is not tolerated by all patients and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea and could be of value in patients intolerant of CPAP. A number of mechanisms have been proposed by which drugs could reduce the severity of OSA. These include an increase in tone in the upper airway dilator muscles, an increase in ventilatory drive, a reduction in the proportion of REM sleep, an increase in cholinergic tone during sleep, a reduction in airway resistance and a reduction in surface tension in the upper airway.
OBJECTIVES
To determine the efficacy of drug therapies in the treatment of sleep apnoea.
SEARCH STRATEGY
We carried out searches on the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2005.
SELECTION CRITERIA
Randomised, placebo controlled trials involving adult patients with confirmed OSA . We excluded trials if continuous positive airways pressure, mandibular devices or oxygen therapy were used. No restriction was placed upon publication language or trial duration.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed studies for inclusion, undertook data extraction according to pre-specified entry criteria, and quality assessment of studies. No response for further information was forthcoming from study authors. Results were expressed as mean differences and 95% Confidence Intervals (CI).
MAIN RESULTS
Twenty-six trials of 21 drugs, involving 394 participants contributed data to the review. Most of the studies were small and many trials had methodological limitations. Each of the studies states that the subjects had OSA but diagnostic criteria were not always explicit and it is possible that some patients with central apnoeas may have been recruited. Six drugs had some impact on OSA severity and two altered daytime symptoms. One study reported that apnoea hypopnea index (AHI) was lower following treatment with intranasal fluticasone compared with placebo (23.3 versus 30.3) in 24 participants with sleep apnoea and rhinitis. Subjective alertness in the daytime also improved. Physostigmine gave an AHI of 41 compared to 54 on placebo (10 participants) and in a similar study Mirtazipine 15 mg produced an AHI of 13 compared to 23.7 for placebo (10 participants). Topical nasal lubricant given twice overnight resulted in an AHI of 14 compared to 24 with placebo (10 participants). These three latter studies were of single night crossover design and so there are no data on the acceptability of these treatments or their effect on symptoms. Paroxetine was shown to reduce AHI to 23.3 compared to 30.3 for placebo, most of the 20 participants tolerated the treatment but there was no improvement in daytime symptoms. Acetazolamide also reduced the AHI (one crossover trial of nine patients, mean difference 24 (95% CI 4 to 44). However there was no symptomatic benefit from the drug and it was poorly tolerated in the long term. Protriptyline led to a symptomatic improvement (improved versus not improved) in two out of three crossover trials (13 participants, Peto Odds Ratio 29.2 (95% CI 2.8 to 301.1) but there was no change in the apnoea frequency. In one trial naltrexone did reduce AHI, but total sleep time favoured placebo. No significant beneficial effects were found for medroxy progesterone, clonidine, mibefradil, cilazapril, buspirone, aminophylline, theophylline doxapram, ondansetron or sabeluzole.
AUTHORS' CONCLUSIONS
There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short-term outcome. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24 and 45%. For fluticasone, mirtazipine, physostigmine and nasal lubricant, studies of longer duration are required to establish whether this has an impact on daytime symptoms. Individual patients had more complete responses to particular drugs. It is likely that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study.
Topics: Humans; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive
PubMed: 16625567
DOI: 10.1002/14651858.CD003002.pub2 -
Paediatric Drugs Aug 2020Caffeine is a common treatment for neonatal intensive care management of the developmental complication of apnea of prematurity in preterm infants. There are several...
BACKGROUND
Caffeine is a common treatment for neonatal intensive care management of the developmental complication of apnea of prematurity in preterm infants. There are several systematic reviews (SRs) on the performance of caffeine in the treatment of apnea. The evidence provided by those, however, is depressed by an information overload due to high heterogeneity in the characteristics as well as the quality of these SRs.
OBJECTIVE
The aim was to provide a systematic overview of SRs on the use of caffeine for the management of neonatal apnea. Such overviews are a recent method used to assess and filter top evidence among SRs, enabling enhanced access to targeted information of interest.
METHODS
A comprehensive literature search was conducted via EMBASE, Cochrane Database of Systematic Reviews (CDSR), and PubMed since inception to January 2020. Two reviewers independently conducted study selection and data extraction, and assessed the quality of methods and the risk of bias in included SRs based on A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) and Risk of Bias in Systematic Reviews (ROBIS) tools. Extracted data related to study type, characteristics, patients, intervention, comparator, regimen, and outcome measures.
RESULTS
Seven SRs with meta-analyses (SRMAs) were included in the current overview, involving a total of 63,315 neonates. SRMAs included randomized clinical and observational studies, with various types of patients, comparators, and outcomes. The quality of SRMAs ranged from critically low (n = 1), low (n = 1), moderate (n = 2), to high (n = 3), and the risk of bias was unclear (n = 2), low (n = 4), and high (n = 1). The effectiveness of caffeine with regard to treatment success and the rate of apnea was not significantly different from that of theophylline or doxapram in two SRMAs. Against control, in one SRMA, while caffeine reduced the rate of failure as well as the need for pressure ventilation, it did not significantly reduce mortality. This comparative effectiveness of caffeine was based on high-quality SRMAs with a low risk of bias. The effectiveness against apnea seems to be enhanced via the administration of early (0-2 days) or high doses of caffeine in one and three SRMAs, respectively. This, nevertheless, was based on lower-quality SRMAs with a higher risk of bias. Safety outcomes were mostly based on comparative SRMAs of different drug regimens, whereby, less tachycardia and lower risk for complications were reported with lower and earlier caffeine administrations, respectively. The evidence behind this, however, was limited in quantity and quality.
CONCLUSION
While limited in quantity, there is evidence of non-inferior effectiveness of caffeine against other methylxanthines or doxapram for the management of apnea in neonates. Owing to the limited quality, however, limited evidence exists in support of an optimal administration regimen for caffeine. Further controlled studies are, therefore, needed to confirm the comparative usefulness of caffeine as well as to assess its different potential regimens, including in relation to safety.
Topics: Apnea; Caffeine; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Randomized Controlled Trials as Topic; Theophylline; Treatment Outcome
PubMed: 32488731
DOI: 10.1007/s40272-020-00404-4 -
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