Summary of findings
Description of the condition
Supraventricular tachycardia (SVT) is a generic term applied in reference to any tachycardia originating above the ventricles and which involves atrial tissue or atrioventricular (AV) nodal tissue (Medi 2009). It encompasses such arrhythmias as atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia (Wolff Parkinson White Syndrome), atrial flutter, atrial fibrillation and the sinus tachycardias. More specificity can be applied when SVT is used to describe those tachycardias which involve a nodal dependent re-entrant circuit, such as that found in atrioventricular nodal re-entrant tachycardia (AVNRT) or atrioventricular re-entrant tachycardia (AVRT) (Medi 2009). The incidence of SVT in the United States of America is approximately 35 cases per 100,000 population annually, with a prevalence of approximately 2.25 cases per 1000 population (Medi 2009). No data were identified to indicate incidence and prevalence in other regions.
These arrhythmias result from the establishment of a re-entry circuit within (or inclusive of) the atrioventricular node. They are usually episodic in nature and may result in the patient exhibiting signs and symptoms ranging from tachycardia or palpitations, shortness of breath, chest pain, anxiety, nausea and dizziness to presyncope/syncope as a consequence of reduced cardiac output (McGuire 2007; Scheinman 2005; Wellens 2003). It is these symptoms which usually precipitate an ambulance request or attendance at hospital. The establishment of AVNRT is believed to occur as a result of a premature atrial complex delivered across the AV node during the relative refractory period. As a consequence of the identification of dual nodal tract pathways for conduction of atrial impulses (fast depolarisation with slow repolarisation and slow depolarisation with fast repolarisation) (Akhtar 1993; Delacretaz 2006; McGuire 2007; Scheinman 2005; Wellens 2003), it is believed that this atrial ectopic complex stimulates a re-entry circuit.
The mechanism of AVRT differs in the existence of accessory pathways (Bundles of Kent). These conductive accessory pathways pass through the atrioventricular septum and thus provide for a larger re-entry circuit, albeit one which passes through the AV node and is similarly affected by increased vagal tone (McGuire 2007; Scheinman 2005; Wellens 2003).
A range of therapies (vagal manoeuvres, pharmacological therapy or synchronised direct current countershock therapy) are employed within emergency medicine and prehospital emergency care practice, in order to extend the refractoriness of AV nodal tissue which will result in reversion of the arrhythmia. The use of pharmacologic agents such as adenosine and calcium channel blockers (Verapamil and Diltiazem) are well known and have been the subject of systematic review and meta-analysis to determine their levels of effectiveness in this setting (Delaney 2011; Holdgate 2009). Synchronised direct current countershock therapy is generally reserved for those patients who are rapidly decompensating as a consequence of the arrhythmia and although the evidence is somewhat limited within the literature, there is support for this practice globally within medical circles. Vagal manoeuvres have also been employed for some time, with demonstrated effectiveness in reverting AVNRT and AVRT of between 12% and 54% (with a median of 25%) across the range of studies conducted (Lim 1998; Mehta 1988; Taylor 1999; Wen 1998).
The arrhythmia is usually transient and may be precipitated by such factors as cardiac disease, stimulant use, electrolyte imbalance and stress. In certain circumstances the frequency of episodes or consequences of episodic poor perfusion associated with SVT may require more significant therapies such as beta blockers or radio frequency ablation in order to improve patient quality of life. Recent studies have also identified increased troponin I enzyme levels (0.02 ng/dL to 1.05 ng/dL, mean 0.20 ng/dL) in patients suffering episodic SVT in the absence of infarction, and although no studies have quantified the potential for patient harm at this time, it is suggested that these elevated troponin I levels may be linked with myocardial damage (Carlberg 2011; Redfearn 2005; Zellweger 2003). These studies also suggest that enzyme levels rise with increasing age of the patient, although the consequences are again at this time unquantified (Carlberg 2011; Redfearn 2005; Zellweger 2003).
Description of the intervention
The Valsalva Manoeuvre was first published by Antonio Maria Valsalva in 1704, in his seminal work De Aura Humane Tractatus, as a means of expelling pus from the middle ear of a patient (Jellinek 2006; Junqueira 2007; Waxman 1980; Yale 2005). It has continued to retain relevance in modern medicine across a range of medical and scientific disciplines. Although it is unclear exactly when the manoeuvre was first applied to terminating haemodynamically stable SVT (in the form of AVNRT or AVRT), it is likely to have coincided with the advent of the ECG (Einthoven 1906). The Valsalva Manoeuvre constitutes three specific elements in order to provide a maximum effect, as follows (Taylor 2004).
- Posture of the patient (supine).
- Pressure generation within the intrathoracic cavity (40 mmHg).
- Duration of strain (15 seconds).
These elements provide a set of values which, when adhered to, should maximise parasympathetic (vagal) response and cause reversion of the arrhythmia (in the absence of any compliance or other patient issues which may affect performance or the nature of effect).
The Valsalva Manoeuvre is defined by four phases of activity, first described by Hamilton et al in 1936, as follows (Junqueira 2007).
- Phase one can be defined by a transient increase in pressure within the thoracic aorta, coupled with a compensatory decrease in heart rate triggered by the baroreceptors within the aortic arch. This pressure increase results from the compressive effect of the generated intrathoracic pressure on the thoracic aorta.
- Phase two is defined by the end of this transient period, resulting in decreasing aortic pressure and increasing heart rate.
- Phase three occurs at the end of the strain phase of the VM (and includes a resulting decrease in intrathoracic pressure exerted on the aorta), leading to a brief pressure drop within the aorta and a compensatory rise in heart rate.
- Phase four occurs as a result of increased venous return and a subsequent increase in preload, resulting in increased aortic pressure as cardiac output is elevated, and a compensatory decrease in heart rate.
The Valsalva Manoeuvre has been selected for review as it provides a simple, quantifiable (method) and non-invasive means of inducing increased vagal tone. Other manoeuvres such as Carotid Sinus Massage and Dive Reflex therapy have limitations within the prehospital setting regarding patient safety, standardisation and reproducibility, and the logistics of application (for example, the acquisition and use of ice).
How the intervention might work
The Valsalva Manoeuvre is a simple, quantifiable and non-invasive method of increasing vagal tone; thereby increasing the refractory period of myocardial cells in order to terminate the established nodal re-entry circuit. The manoeuvre was traditionally performed by expiring against a closed glottis to increase intrathoracic pressure, thereby triggering baroreceptor activity and increased vagal tone. However, this also has potentially deleterious side effects such as increased intra-occular pressure and profound hypotension as a consequence of unfettered vagal stimulation (Junqueira 2007; Looga 2004; Taylor 2004; Vaisrub 1974). Since Rushmer introduced the measurement of intraoral pressure in 1947 (Junqueira 2007), the manoeuvre is now more commonly described and instructed as an exhalation against a defined pressure (measurable) in order to avoid significant side effects and to improve performance and patient safety. Maximum vagal response occurs on release of the sustained intrathoracic pressure, which occurs in phase four of the VM, and it is at this point that reversion of the arrhythmia is most likely to occur (Looga 2004; Waxman 1980). Recently, efforts have been made to provide a standard of instruction of the VM for use in the haemodynamically stable patient suffering AVNRT, including the use of a 10 ml syringe to generate the 40 mmHg pressure required (Taylor 2004; Smith 2009a).
Why it is important to do this review
Currently, there are a plethora of definitions of Valsalva performance and it is used across a variety of medical and scientific disciplines to promote different effects (cardiac or non-cardiac) (Smith 2009b). The effectiveness of the VM is challenged by available interventional and observational non-randomised clinical studies (7.3% to 54% of study sample) (Taylor 1999; Waxman 1980; Taylor 2004) and the plethora of definitions of method (specifically variations in the three elements of posture, pressure and duration) (Smith 2009b). Through this review, we hoped to ascertain the nature of evidence available to demonstrate VM effectiveness, and the need for further study to define the effectiveness of the VM for the development of future therapy regimens in the treatment of SVT.
To assess the evidence of effectiveness of the Valsalva Manoeuvre in terminating supraventricular tachycardia.
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) of VM effectiveness in terminating SVT.
Types of participants
Participants whose normal cardiac rhythm is sinus rhythm and who have no known cardiac disease, with acute onset or induced episodes of haemodynamically stable atrioventricular nodal reentrant tachycardia (AVNRT) or atrioventricular reentrant tachycardia (AVRT).
Types of interventions
The definition of a Valsalva Manoeuvre for the purpose of this review is a physical manoeuvre which has three elements (posture, strain duration and pressure), and when performed results in an increase in intrathoracic pressure and increased refractoriness of AV nodal tissue. Although the model of practice described within the Intervention Description is preferred, a range of values are currently used within the literature to describe the Valsalva Manoeuvre. As such, we accepted the following values for this review:
- posture (supine, or supine with legs elevated);
- strain duration (15 to 30 seconds);
- pressure (30 mmHg to 50 mmHg).
Comparison: Only those study results identifying the effectiveness of the VM for SVT reversion were included in this review, whilst reported comparisons of effectiveness of VM with other vagal manoeuvres (such as Carotid Sinus Massage or Dive Reflex) within included studies were excluded in accordance with the aims of the review.
Types of outcome measures
Studies were eligible for inclusion if they reported any of the following outcome measures:
Reversion of SVT to a sinus rhythm.
1. Failure to revert SVT to a sinus rhythm, followed by:
- repeated attempts at VM or other vagal manoeuvres;
- pharmacological intervention; or
- direct current countershock therapies.
2. Cardiovascular effects of VM performance (e.g. hypotension, bradycardia).
3. Frequency and severity of adverse events resulting from application of the VM.
4. Mortality resulting from the VM.
Search methods for identification of studies
We searched the following sources:
- Cochrane Central Register of Controlled Trials (CENTRAL), in The Cochrane Library, Issue 1 of 12 (2012).
- MEDLINE OVID (1946 to January Week 3 2012).
- EMBASE & EMBASE Classic OVID (1947 to 2012 Week 04).
- Conference Proceedings Citations Index (ISI Web of Science) (1970 to 27 January 2012).
- Conference abstracts (ISI BIOSIS Previews) (1969 to 27 January 2012).
We also searched for adverse events using:
- MEDLINE OVID (1946 to January Week 3 2012).
The search strategies are presented in Appendix 1. There were no language restrictions applied to the searches.The MEDLINE and EMBASE strategies were combined with the Cochrane sensitive-maximising RCT filter (Lefebvre 2011).
Searching other resources
- World Health Organization International Clinical Trials Registry Platform (ICTRP): http://apps.who.int/trialsearch/default.aspx (Search terms used: Valsalva, Manoeuvre. Accessed 22 February 2012).
- Clinical Trials Registry: http://www.anzctr.org.au/TrialSearch.aspx (Search terms used: Valsalva, Manoeuvre. Accessed 22 February 2012).
We also handsearched the following literature:
- Index to Theses.
- International Standard Randomised Controlled Trial Number Register (ISRCTN).
- The bibliographies of all relevant publications identified by the electronic and handsearches.
Data collection and analysis
Selection of studies
The search results (titles and abstracts) were screened by two authors (GS and KD). The results from the search strategy are presented as a flowchart (Figure 1) based on the Quorum statement (Lefebvre 2011). Titles and abstracts identified by the search strategy were screened independently by both reviewers. All potentially relevant studies were retained and the full texts of these studies were examined to determine which studies satisfied the inclusion criteria. A two stage process was used to select studies for inclusion: (i) independent selection (without blinding) by two authors (GS and KD) to short list potential studies, (ii) a final group selection involving discussion between two authors (GS and KD) to define which studies met the inclusion criteria. Arbitration by a third author to resolve any disagreements was not required.
|Figure 1. Search results|
Data extraction and management
Data extraction was carried out independently by the same reviewers using pre-defined data extraction forms. No RCT studies were identified requiring translation to English. No important data were missing which would require contacting the original authors of the study for clarification. Data extraction was performed by two authors (GS and KD) independently without blinding and using a paper data collection form to record and tabulate search results. The results were compared, discussed and collated prior to being transcribed to an electronic spreadsheet for tabulation. There were no disagreements regarding applicability for inclusion or exclusion.
Assessment of risk of bias in included studies
We used the risk of bias assessment guidelines in the Cochrane Handbook for Systematice Reviews of Interventions (Higgins 2011) to address the following sources of potential bias:
- selection bias;
- performance bias;
- attrition bias; and
- detection bias.
Each of these was addressed using a three point grading (high, unclear, or low) to measure the following:
- allocation concealment (did the method enable concealment to the point of assignment);
- blinding to outcome assessment (where the investigators were aware of the treatment allocation);
- adequacy of controls (did the study provide for equal numbers of treatment and control subjects);
- adequacy of follow up (did the method account for all participants including withdrawal, dropout or protocol deviation);
- intention-to-treat analysis (did the study provide for post-treatment bias control through an intention-to-treat analysis, follow up of withdrawals and completeness, and analysis of results by original treatment and treatment given).
A third author (AM) arbitrated any disagreement regarding risk or bias assessment.
Measures of treatment effect
Unit measures were assigned using common terms to all papers as follows:
- reversion rate;
- time to reversion (number of VM attempts);
- relapse rate;
- minor adverse events;
- major adverse events.
Unit of analysis issues
The unit of analysis was the individual participant. Consultation with an appropriately qualified statistician was not required as no unit of analysis issues arose.
Dealing with missing data
Contact with the study authors was not required as no data were missing.
Assessment of heterogeneity
The presence of high levels of clinical and methodological heterogeneity resulted in studies being presented using descriptive statistics only.
Assessment of reporting biases
Measurement of reporting bias was assessed by the following:
- clear definition of inclusion/exclusion criteria;
- clear definition of outcome measure(s);
- reported accuracy, precision and observer variation of outcome measures;
- appropriately timed outcome measures.
We were unable to synthesise data statistically and results are demonstrated using descriptive statistics only.
Subgroup analysis and investigation of heterogeneity
Subgroup analysis was not undertaken due to insufficient specific data within the available studies.
No sensitivity analysis was possible, as no meta-analysis was undertaken due to high level clinical and methodological heterogeneity. Descriptive statistics were used to present results.
Description of studies
Results of the search
The literature search identified 609 potentially relevant studies. After filtering for duplication, 169 studies were excluded. Each of the remaining 440 studies were examined (title and abstract), and those which were either not an RCT or which did not demonstrate effectiveness of VM in reverting SVT were excluded. Three studies were retrieved for more detailed evaluation and were subsequently included in the review. The literature search results are described graphically in Figure 1. Two studies (Mehta 1988; Wen 1998) included a cross-over design where an alternative intervention was used irrespective of primary intervention success. The Lim 1998 study was also a cross-over design, where subsequent intervention was dependent upon failed primary intervention in reversion of SVT. This offered challenges in providing analysis appropriate for the question of VM effectiveness in terminating SVT, as each RCT used varied methodology (multiple attempts of a variety of vagal manoeuvre interventions and performance techniques). As a result, heterogeneity of methods precluded meta-analysis. It was not possible to provide descriptions of reported adverse effects of VM used in the management of SVT as none were identified as a result of the search. The results of the adverse effects search are described graphically in Figure 2.
|Figure 2. Search results for adverse effects|
The three selected RCTs were conducted in three different countries (Singapore, England and Taiwan), and comprised 316 participants. All three studies reported a primary outcome measure of reversion (or effectiveness) of VM used in terminating SVT. Each study included application of the VM between one and three times to achieve effect. All studies included a cross-over design and the nature of this design enabled descriptive analysis of two of these (Mehta 1988; Wen 1998). The Lim 1998 study reported patients in the clinical setting presenting with SVT to an emergency department, whereas the Mehta 1988 and Wen 1998 studies described induced SVT in participants with significant control of other variables (such as cessation of medication for adequate half-life time prior to participation in the study). It is possible that an induced SVT (by programmed electrical stimulation) in a healthy adult may be more susceptible to reversion by vagal manoeuvres than a patient presenting to hospital who is experiencing an episode of SVT (of varied duration). The use of induced SVT may not represent clinical presentations of SVT, as an arrhythmia generated by a period of external electrical stimulation is likely to self resolve more rapidly than one which is triggered or maintained by a stimulus from within the myocardium, although this is not clearly evidenced within the available literature. As a consequence, the reversion rate demonstrated by the Lim 1998 study is more likely to represent clinical effectiveness. It is also likely that individuals who have a history of SVT are more likely to be familiar with the VM and its correct application. This suggests that these individuals would be more likely to be adept at applying the VM than healthy participants within the two laboratory studies, which may affect the results of these studies. It was not possible to gauge the potential effect of this factor within this review. Also, given the cross-over design of each study, this review data represents primary intervention (VM) reversion within the available RCT data, and is not affected by other vagal manoeuvres. It was decided that both the Mehta 1988 and Wen 1998 studies provided an appropriate inclusion defined by the review question, whilst the Lim 1998 study added value as a clinical application of VM in patients presenting with SVT to an emergency department and so is presented separately.
No identified RCTs were excluded.
Risk of bias in included studies
The details of quality assessment based upon the Cochrane Handbook for Systematic Reviews of Interventions method (Higgins 2011) are presented in the table 'Characteristics of included studies'. In addition, a brief analysis of the risk of bias of included studies can be found below. No studies demonstrated adequate allocation concealment. In addition, blinding was not possible due to the nature of the intervention.
There is a high risk of selection bias within the Medi 2009 and Wen 1998 studies, as allocation concealment was not reported. The Lim 1998 study contained an unclear risk of selection bias as the use of cards in an envelope (to be selected by a staff nurse) with the intervention written on each appears inadequate to demonstrate appropriate random allocation of participants to intervention.
There was no evidence of blinding in any of the three studies included in this review. It is worth noting that the nature of the intervention (performance of a vagal manoeuvre) prevents blinding of investigators or participants to either intervention or effect. Thus, performance bias was not practical within the three studies and detection bias was not reported in any of the three studies.
Incomplete outcome data
There was a low risk of attrition bias within all of the three studies included in this review, as results included outcome reporting for all participants in each study.
There was a low risk of reporting bias within all of the three studies included in this review, as all outcomes for each intervention were reported in all cases.
Other potential sources of bias
Effects of interventions
Each of the three identified RCT studies used a cross-over design to compare effectiveness of the VM against other vagal manoeuvres (the dive reflex (HDR) and carotid sinus massage (CSM)). As this review was specifically to address the effectiveness of VM for SVT reversion, its comparative effect against other vagal manoeuvres has not been assessed or analysed here. Also, heterogeneity of method between studies would make such a comparison difficult. All three RCTs provided adequate data on the primary outcome of the review (termination of SVT) and as a consequence, the study investigators were not contacted for further information by the authors of this review. The data within the included RCT studies did not provide an opportunity to report on reversion success, adverse effects and mortality outcomes. The absence of reported data prevented other listed outcomes from being assessed. Those outcomes which were able to be assessed are reported as follows.
The Mehta 1988 and Wen 1998 studies provided reversion success rates of 54.3% (19/35) and 45.9% (61/133), respectively, whilst the Lim 1998 study reported reversion success of 19.4% (12/62). Statistical pooling was not possible as a result of heterogeneity between included studies.
We were unable to calculate the nature of significant cardiovascular effects, such as hypotension and bradycardia resulting from VM application to SVT, as these were not reported. Within the Lim 1998 study, a single patient was reported to be diagnosed with myocardial infarction, but it is unclear if this was the result of the SVT or precipitated the arrhythmia.
No deaths were reported in any of the studies. As a consequence, the mortality rate for VM use in SVT within this review is zero.
Summary of main results
The Mehta 1988 and Wen 1998 studies provided reversion success rates of 54.3% (19/35) and 45.9% (61/133), respectively, whilst the Lim 1998 study reported reversion success of 19.4% (12/62). There were important methodological differences and significant heterogeneity between the studies which prevented meta-analysis. Also, sufficient validity could not be ascribed to the primary studies. This has resulted in only descriptive statistics for VM reversion of SVT being reported.
Side effects, cardiovascular effects and mortality associated with VM use for SVT were not reported in the three included studies, precluding reporting or analysis.
Overall completeness and applicability of evidence
The data on the primary outcome were available for analysis. The identified studies specifically assessed the effectiveness of the VM in reverting SVT and so were applicable. It was noted that two of the studies (Mehta 1988; Wen 1998) provided assessment in the setting of induced SVT, whereas the third study assessed the effectiveness of VM in patients presenting to an emergency department with an episode of SVT. This third study offered more relevant data for the clinical setting. Though the identified studies are somewhat dated, it is unlikely that we have failed to detect a relevant study given the comprehensive search strategy.
Quality of the evidence
The quality of evidence was generally poor, as a consequence of sample size and number of available RCTs. Also, the nature of variability in performance of (and indeed what quantified) a VM for this application ensured that it was not possible to make a definitive analysis of effectiveness of the VM for termination of SVT. Whilst all three studies provided a primary outcome (reversion), there was little or no information regarding other outcomes (mortality, adverse effects and cardiovascular effects). Precision of the results is low, with confidence intervals specific to reversion not reported in two studies. Generalisability is challenged by the setting of the Mehta 1988 and Wen 1998 studies, and the Lim 1998 study provides the only example of clinical applicability.
At this time there is no universally accepted standardised VM, although the method stated within the Description of the intervention section is often used in the clinical setting. Future studies should consider using this method to improve homogeneity between studies and the generalisation of results.
Potential biases in the review process
Agreements and disagreements with other studies or reviews
There is insufficient evidence available to determine if these review findings represent concurrence, as there are no other systematic reviews of this intervention.
Implications for practice
The results of the three RCTs examined within this review are insufficient to support a definitive assessment of effectiveness for use of the VM to terminate SVT in patients with this condition. However, given the reversion rates of 54.3% and 45.9% in the laboratory studies, and 19.4% within the clinical study, it is possible to suggest that the VM should be considered useful as a safe (in the absence of and reporting of adverse effect data), non-invasive first-line measure for attempting reversion of haemodynamically stable SVT prior to the use of pharmacological interventions. The reversion rate of the third (clinical) study is less than those of the induced SVT studies, and this leads us to believe that reversion success of the VM for SVT is likely to lie in the lower realm of the results demonstrated.
Implications for research
There are opportunities to improve the quality of available evidence described by this review. The prevalence of patients presenting with SVT enables large sample sizes to be readily obtained for future studies, demonstrating a methodological rigour. Consideration should be given to the development and acceptance of a standardised VM for the termination of SVT, as this would aid in improving homogeneity between studies. There is also a need to identify factors which may impact upon VM effectiveness (such as diabetes mellitus, hypertension and CAD), the impact of age on parasympathetic tone generation, the impact of respiratory disease (such as COPD and asthma) on the patients' ability to generate appropriate intrathoracic pressure for a VM, and future studies should consider the following:
Sharon Kramer, Systematic Review Trainer, Australasian Cochrane Centre, for her invaluable assistance in guiding the authors through the review process.
Data and analyses
This review has no analyses.
Appendix 1. Primary search strategy
#1 MeSH descriptor Valsalva Maneuver, this term only
#3 MeSH descriptor Vagus Nerve explode all trees
#5 MeSH descriptor Vagus Nerve Stimulation, this term only
#7 (#1 OR #2 OR #3 OR #4 OR #5 OR #6)
#8 MeSH descriptor Tachycardia, Supraventricular explode all trees
#9 MeSH descriptor Tachycardia, Paroxysmal, this term only
#10 MeSH descriptor Tachycardia, Reciprocating explode all trees
#11 (supraventric* near/4 arrhythmi*)
#12 (supra-ventric* near/4 arrhythmi*)
#18 (#8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17)
#19 (#7 AND #18)
1 Valsalva Maneuver/
3 exp Vagus Nerve/
5 Vagus Nerve Stimulation/
8 exp Tachycardia, Supraventricular/
9 Tachycardia, Paroxysmal/
10 exp Tachycardia, Reciprocating/
11 (supraventric* adj4 arrhythmi*).tw.
12 (supra-ventric* adj4 arrhythmi*).tw.
19 7 and 18
20 randomised controlled trial.pt.
21 controlled clinical trial.pt.
24 drug therapy.fs.
28 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27
29 exp animals/ not humans.sh.
30 28 not 29
31 19 and 30
1 Valsalva Maneuver/
3 exp Vagus Nerve/
5 Vagus Nerve Stimulation/
8 exp Tachycardia, Supraventricular/
9 Tachycardia, Paroxysmal/
10 exp Tachycardia, Reciprocating/
11 (supraventric* adj4 arrhythmi*).tw.
12 (supra-ventric* adj4 arrhythmi*).tw.
19 7 and 18
23 cross over$.tw.
26 (doubl$ adj blind$).tw.
27 (singl$ adj blind$).tw.
31 crossover procedure/
32 double blind procedure/
33 randomized controlled trial/
34 single blind procedure/
35 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34
36 (animal/ or nonhuman/) not human/
37 35 not 36
38 19 and 37
Web of Science & BIOSIS Previews
# 15 #14 AND #13
# 14 Topic=((random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross-over*))
# 13 #12 AND #4
# 12 #11 OR #10 OR #9 OR #8 OR #7 OR #6 OR #5
# 11 Topic=(tachycardi*)
# 10 Topic=(avnrt)
# 9 Topic=(avrt)
# 8 Topic=(svt)
# 7 Topic=(tachyarrhythmi*)
# 6 Topic=(supra-ventric* near/4 arrhythmi*)
# 5 Topic=(supraventric* near/4 arrhythmi*)
# 4 #3 OR #2 OR #1
# 3 Topic=(vagus)
# 2 Topic=(vagal)
# 1 Topic=(valsalva*)
Appendix 2. Primary adverse effects search strategy
MEDLINE (OVID) search strategy filter for adverse effects as per the Loke 2011 method described within the Cochrane Handbook for Systematic Reviews of Interventions:
1. Valsalva Maneuver/ae
2. exp Vagus Nerve/ae
3. Vagus Nerve Stimulation/ae
9. adverse effect*.tw
10. side effect*.tw
18. 8 AND 17
19. 1 OR 2 OR 3 OR 18
20. supraventricular tachycardia*.tw
21. 19 and 20
Contributions of authors
GS, KD and AM (protocol preparation, data search, data acquisition, data filtering, preparation of final report, and update of review).
GS, KD, DT, AM and KC (data analysis).
Declarations of interest
The authors declare no interest, financial or otherwise in the completion, conduct or outcomes of this review.
Differences between protocol and review
As no RCT studies were identified with participants aged > 18 years only, it was unanimously decided that the protocol should be varied to enable inclusion of those studies which included paediatric participants to enable this review to report what is currently known.
Due to the nature of identified RCT studies included in this review, it was necessary to change both the title and objectives of the review to remove the terms "in the prehospital and emergency medicine settings" which reflects more appropriately what was able to be assessed from within the published evidence.
The adverse effects search strategy differs between protocol and review. As a result of the VM being used as a therapeutic and diagnostic tool across many scientific and medical disciplines, it was necessary to make changes to the adverse effects search strategy in order to refine the results to VM application to the SVT setting.
Medical Subject Headings (MeSH)
MeSH check words
* Indicates the major publication for the study