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The Cochrane Database of Systematic... Oct 2004Pulmonary Hypertension (PH) can be either of unknown aetiology (primary pulmonary hypertension (PPH)) or due to a known underlying cause (secondary pulmonary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pulmonary Hypertension (PH) can be either of unknown aetiology (primary pulmonary hypertension (PPH)) or due to a known underlying cause (secondary pulmonary hypertension (SPH). Pulmonary arteriolar vasoconstriction is considered to be an important characteristic of PH. Therapies which aim to vasodilate are used to treat pulmonary hypertension.
OBJECTIVES
To determine the clinical efficacy of sildenafil, a vasodilator which works through inhibition of the enzyme phosphodiesterase type V (PDE5I), administered via any route to people with pulmonary hypertension in primary or secondary forms.
SEARCH STRATEGY
Electronic databases were searched with pre-defined search terms. Searches were current as of November 2003.
SELECTION CRITERIA
Randomised controlled trials were considered for inclusion in the review. We included studies which assessed the effects of sildenafil in participants with PPH and SPH.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed and extracted data from clinical trials. Data were entered in RevMan Analyses 1.0.2. Continuous data were pooled with an estimate on either WMD (weighted mean difference) or SMD (standardised mean difference) scales. Dichotomous data were pooled and a RR (relative risk) was calculated.
MAIN RESULTS
Four studies recruiting 77 participants met the inclusion criteria of the review. Two studies assessed the acute effects of sildenafil. Two small crossover study assessed the effects of long term administration. The 'acute effect' studies indicated that sildenafil has a pulmonary vasodilatory effect. The two crossover studies showed improvement in symptoms. One study showed improvement in fatigue domains from a validated health status questionnaire. Both crossover studies reported that the drug was well tolerated.
REVIEWERS' CONCLUSIONS
The validity of the observed effects is undermined by small participant numbers and inadequate exploration of the different disease etiologies. The effects on long term outcome such as NYHA functional class, symptoms, mortality and exercise capacity require further validation. More studies of adequate size are required before the long term effects of sildenafil on clinically important outcomes can be established.
Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Humans; Hypertension, Pulmonary; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Vasodilator Agents
PubMed: 15495058
DOI: 10.1002/14651858.CD003562.pub2 -
The Cochrane Database of Systematic... 2004Theophylline causes potent cerebral vasoconstriction which decreases blood flow in the non-ischaemic areas of the brain and increases collateral blood flow surrounding... (Review)
Review
BACKGROUND
Theophylline causes potent cerebral vasoconstriction which decreases blood flow in the non-ischaemic areas of the brain and increases collateral blood flow surrounding the ischaemic region. NOTE: This review covers an area where no active research is taking place. It will be updated if relevant information becomes available, e.g. on completion of an appropriate study.
OBJECTIVES
The objective of this review was to assess the effect of theophylline and its analogues, aminophylline and caffeine, in people with confirmed or presumed acute ischaemic stroke.
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (last searched November 2003). For the first version, we also searched EMBASE (1980 to 1999), MEDLINE (1966 to 1999) and Science Citation Index (1981 to 1999). We also contacted the principal investigators of the identified trials.
SELECTION CRITERIA
Randomised trials of theophylline or an analogue compound compared with placebo or control in people with confirmed or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset.
DATA COLLECTION AND ANALYSIS
Three reviewers applied the inclusion criteria, assessed trial quality and extracted data for the first version. The review was updated by one reviewer.
MAIN RESULTS
Two trials involving just 119 patients were included; 6 studies were excluded. Trial quality was good. Both of the trials tested aminophylline. Analysis was by intention-to-treat where possible. No significant difference was shown in early case fatality (within four weeks) between aminophylline and placebo although the confidence intervals were wide (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.49 to 2.56). There was no significant difference for early death and deterioration (OR 0.87, 95% CI 0.41 to 1.88). Death or disability was not significantly reduced by treatment based on 73 patients in one trial (OR 0.64, 95% CI 0.24 to 1.68). Data for late death and disability were not in a form suitable for analysis. No data on quality of life were available.
REVIEWERS' CONCLUSIONS
There is not enough evidence to assess whether theophylline or its analogues, e.g. aminophylline, are safe and improve outcome in people with acute ischaemic stroke.
Topics: Aminophylline; Brain Ischemia; Caffeine; Humans; Randomized Controlled Trials as Topic; Stroke; Theophylline; Vasodilator Agents
PubMed: 15266427
DOI: 10.1002/14651858.CD000211.pub2 -
The Cochrane Database of Systematic... 2000Because hyperventilation is often associated with a rapid fall in intracranial pressure, it has been assumed to be effective in the treatment of severe head injury.... (Review)
Review
BACKGROUND
Because hyperventilation is often associated with a rapid fall in intracranial pressure, it has been assumed to be effective in the treatment of severe head injury. Hyperventilation reduces raised intracranial pressure by causing cerebral vasoconstriction and a reduction in cerebral blood flow. Whether reduced cerebral blood flow improves neurological outcome however, is unclear.
OBJECTIVES
To quantify the effect of hyperventilation on death and neurological disability following head injury.
SEARCH STRATEGY
The search strategy drew on that of the Injuries Group as a whole. The reference lists of all relevant articles identified were checked and the first author of reports was contacted to ask for assistance in identifying any further trials. Most recent search was done in September 1999.
SELECTION CRITERIA
All randomised trials of hyperventilation, in which study participants had a clinically defined acute traumatic head injury of any severity. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
We collected data on the participants, the timing and duration of the intervention, duration of follow up, neurological disability and death. Relative risks (RR) and 95% confidence intervals were calculated for each trial on an intention to treat basis. Timing, degree and duration of hyperventilation were identified a-priori as potential sources of heterogeneity between trials.
MAIN RESULTS
One trial of 113 participants was identified. Hyperventilation alone, as well as in conjunction with the buffer THAM showed a beneficial effect on mortality at one year after injury, although the effect measure was imprecise (RR=0.73; 95% CI 0.36;1.49 and RR=0.89; 95% CI 0.47;1.72 respectively). This improvement in outcome was not supported by an improvement in neurological recovery. For hyperventilation alone, the RR for death or severe disability was 1. 14 (95% CI 0.82;1.58). The RR for death or severe disability in the hyperventilation plus THAM group, was 0.87 (95% CI 0.58;1.28).
REVIEWER'S CONCLUSIONS
The data available are inadequate to assess any potential benefit or harm that might result from hyperventilation in severe head injury. Randomised controlled trials to assess the effectiveness of hyperventilation therapy following severe head injury are needed.
Topics: Brain Injuries; Humans; Hyperventilation; Respiration, Artificial
PubMed: 10796728
DOI: 10.1002/14651858.CD000566 -
The Cochrane Database of Systematic... 2000Following a period of mechanical ventilation, post-extubation upper airway obstruction can occur in newborn infants, especially after prolonged, traumatic or multiple... (Review)
Review
BACKGROUND
Following a period of mechanical ventilation, post-extubation upper airway obstruction can occur in newborn infants, especially after prolonged, traumatic or multiple intubations. The subsequent increase in upper airway resistance may lead to respiratory insufficiency and failure of extubation. The vasoconstrictive properties of epinephrine, and its proven efficacy in the treatment of croup in infants, has led to the routine use of inhaled nebulised epinephrine immediately post-extubation in some neonatal units. It is also recommended for neonates with post-extubation tracheal obstruction and stridor in neonatal and respiratory textbooks and reviews.
OBJECTIVES
The primary objective was to assess whether nebulised epinephrine administered immediately after extubation in neonates weaned from IPPV decreases the need for subsequent additional respiratory support.
SEARCH STRATEGY
Searches were made of Medline (MeSH search terms 'epinephrine' and 'exp infant, newborn'), the Oxford Database of Perinatal trials, expert informants and journal hand searching mainly in the English language, expert informant searches in the Japanese language by Prof. Ogawa, previous reviews including cross references, abstracts, and conference and symposia proceedings.
SELECTION CRITERIA
All randomised and quasi-randomised control trials in which nebulised epinephrine was compared with placebo immediately post-extubation in newborn infants who have been weaned from IPPV and extubated, with regard to clinically important outcomes (i.e. need for additional respiratory support, increase in oxygen requirement, respiratory distress, stridor or the occurrence of side effects).
DATA COLLECTION AND ANALYSIS
No studies met our criteria for inclusion in this review.
MAIN RESULTS
No studies were identified which looked at the effect of inhaled nebulised epinephrine on clinically important outcomes in infants being extubated.
IMPLICATIONS FOR PRACTICE
There is no evidence either supporting or refuting the use of inhaled nebulised racemic epinephrine in newborn infants.
IMPLICATIONS FOR RESEARCH
randomised controlled trials are needed comparing inhaled nebulised racemic epinephrine with placebo in neonates post-extubation. This should be looked at both as a routine treatment post-extubation and as specific treatment for post-extubation upper airway obstruction. Study populations should include the group of infants at highest risk for upper airway obstruction from mucosal swelling because of their small glottic and sub-glottic diameters (ie those infants with birthweights less than 1000 grams).
Topics: Administration, Inhalation; Epinephrine; Humans; Infant, Newborn; Intubation, Intratracheal; Nebulizers and Vaporizers; Racepinephrine; Respiration, Artificial; Respiratory Insufficiency; Vasoconstrictor Agents; Ventilator Weaning
PubMed: 10796376
DOI: 10.1002/14651858.CD000506