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Cochrane Database of Systematic Reviews Protocol - Intervention

The effectiveness of the modified Valsalva Manoeuvre for reversion of supraventricular tachycardia

Authors' declarations of interest

Version published: 21 October 2020 Version history

https://doi.org/10.1002/14651858.CD013762
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Abstract

Objectives

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

To assess the effectiveness of the mVM in terminating SVT.

Background

Description of the condition

Supraventricular tachycardia (SVT) is defined as any tachycardia originating above the ventricles, such as in the atrial tissue or atrioventricular (AV) node (Medi 2009). SVT is a tachycardia with sudden onset, offset, and a regular ventricular response presenting with palpitations, shortness of breath, or chest discomfort (Brugada 2019). Individuals with paroxysmal SVT frequently visit the emergency department (ED) for symptoms such as palpitation, syncope, presyncope, chest pain, or shortness of breath (Medi 2009). The predisposition of SVT patients to frequent ED visits, drug administration, or electrical cardioversion can be costly for the individual and their family, especially in low‐ to middle‐income countries. SVT may present as either narrow QRS or wide QRS tachycardia with regular rhythm, but conventionally includes tachycardias with irregular rhythm, such as atrial fibrillation. The QRS complex refers to the Q wave, R wave, and S wave of an electrocardiogram (ECG), which may represent ventricular depolarisation. QRS duration refers to the time between the Q wave and S wave. In general, the SVT prevalence is 2.25 in 1000 people, and the incidence rate is 35 in 100,000 person‐years (Page 2016). Vagal manoeuvres are therapies that can be used for termination of a narrow QRS SVT (Brugada 2019). We will focus on haemodynamically stable SVT patients because for haemodynamically unstable patients (i.e. patients experiencing shock), synchronised cardioversion is recommended as a first‐line therapy (Brugada 2019).

Description of the intervention

There are several treatments for SVT, including the standard Valsalva Manoeuvre (sVM), vagal manoeuvres other than sVM (e.g. the carotid sinus massage and the diving reflex), electrical or drug cardioversion, ablation, or observation (Brugada 2019). For haemodynamically stable patients, the sVM is the first‐line therapy recommended in the latest European Society of Cardiology (ESC) SVT guidelines because of its simplicity, cost‐effectiveness, and safety (Brugada 2019). SVT treatment with adenosine is useful, but is associated with the adverse effects of chest pain and transient asystole (Innes 2008; Page 2016). AV nodal blocking drugs, such as intravenous (IV) non‐dihydropyridine calcium channel blockers or IV beta blockers, can be used to terminate SVT, but there is a potential for the adverse reaction of hypotension.

The sVM is safe and is traditionally recommended in several guidelines for first‐line SVT therapies that increase vagal stimulation and increases localised acetylcholine (Brugada 2019; Page 2016). As for the sVM mechanism, conduction velocity slows down in the AV node and stops the SVT, especially for AV‐nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) (Wong 2004). The effectiveness of sVM for SVT was previously addressed in a Cochrane Review (Smith 2015). That review, which included three randomised controlled trials (RCTs) with a cross‐over design, evaluated the efficacy of four types of vagal manoeuvres (sVM, right carotid sinus massage, left carotid massage, and the diving reflex) and found that the sVM is the most effective therapy for termination of SVT. Despite the effectiveness of sVM, the success rates varied widely, from 19.4% to 54.3%.

Recently, the addition of supine positioning and passive leg elevation immediately after the Valsalva strain has been documented as the modified Valsalva Manoeuvre (mVM), which increases relaxation phase venous return and vagal stimulation. The mVM has been reported to be more effective than sVM in some RCTs (Appelboam 2015; Ceylan 2019; Chen 2019; Çorbacıoğlu 2017).

How the intervention might work

The sVM increases parasympathetic tone, which slows the conduction in the antegrade slow pathway and makes a blockage in the retrograde fast pathway, regulating heart rate (Medi 2009; Wong 2004). However, the patient's posture has been found to be an important factor affecting the success of the mVM because it increases the venous return and parasympathetic tone more effectively (Çorbacıoğlu 2017). The mVM aides in reversion to sinus rhythm by providing a further surge in venous return through an immediate change of posture by laying the patient flat and lifting their legs.

Why it is important to do this review

The standard Valsalva Manoeuvre is cost‐effective and can be done anywhere, but has proved less successful in real‐world settings. A Cochrane Review on this topic was published in 2015: 'Effectiveness of the Valsalva Manoeuvre for reversion of supraventricular tachycardia' (Smith 2015), and at least one international guideline refers to this review (Brugada 2019). However, the previous systematic review and meta‐analysis only included RCTs using the sVM. Recently, at least four RCTs using the new mVM have been published. No systematic review or meta‐analysis has included this new and possibly more effective treatment. The mVM is quite different from the previous method because it requires a patient position change. The modified approach calls for changing the patient's position from a semi‐recumbent to a supine position, and adding a passive leg raise immediately after the Valsalva strain. This modified approach needs evaluation.

Four RCTs have found the mVM to be more effective than the sVM (Appelboam 2015; Ceylan 2019; Chen 2019; Çorbacıoğlu 2017); however, guidelines still recommend sVM as the first‐line option in SVT treatment (Brugada 2019; Page 2016). A systemic review which includes the mVM must be integrated into the evidence. Furthermore, there are some concerns about the mVM, such as a need for additional staff, changes in admission rates, and possible adverse events, which may include hypotension, asystolic pause, amount of adenosine, nausea, and transient headache. Moreover, calculating procedural costs may help patients in low‐ to middle‐income countries. In this review we will review the effectiveness, adverse events, and report the effect magnitude of the mVM compared to the sVM for the treatment of SVT. 

Objectives

To assess the effectiveness of the mVM in terminating SVT.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) of mVM for SVT. We will include participant‐level RCTs, cluster‐RCTs, and cross‐over trials.  

Types of participants

We will include adults, adolescents, and children diagnosed with acute onset or induced episodes of haemodynamically stable SVT (narrow complex tachycardia with QRS duration < 0.12 second on ECG). There will be no age restriction.

We will exclude participants with the following comorbidities/characteristics: participants whose usual cardiac rhythm is not sinus rhythm and who have cardiac disease, haemodynamically unstable patients (systolic blood pressure less than 90 mmHg or an indication for immediate cardioversion), pregnant women, and participants with dementia.

If there are trials with only a subset of eligible participants, we will include the trial if the majority of participants meet the eligible criteria. Otherwise, we will exclude it. We plan a sensitivity analysis to exclude trials with only a subset of eligible participants to test our decision to include them.

Types of interventions

We will include trials comparing the modified Valsalva Manoeuvre (mVM) with the standard Valsalva Manoeuvre (sVM). The definition of mVM for the purposes of this review is a physical manoeuvre with three elements: 1) posture, 2) strain duration, and 3) pressure. Detailed definitions of the mVM and sVM are shown below. We will permit IV fluid therapy, which has no effect on stopping SVT, as a co‐intervention if it is included in both intervention groups.

Definition of mVM

  1. Sitting position

  2. Valsalva Manoeuvre strain to a pressure of 30 to 50 mmHg or with blowing into a 10‐millilitre syringe in an attempt to move the plunger

  3. Strain duration of 10 to 20 seconds

  4. Posture change: laying the patient down with a leg lift immediately after steps 1 through 3

Definition of sVM

  1. Sitting or supine position

  2. Valsalva Manoeuvre strain to a pressure of 30 to 50 mmHg or with blowing into a 10‐millilitre syringe in an attempt to move the plunger

  3. Strain duration of 10 to 20 seconds 

We will define treatment failure as incapacity to revert to sinus rhythm after the number of attempts deemed required and safe by the investigators of each trial.

Types of outcome measures

Reporting one or more of the outcomes listed here in the trial is not an inclusion criterion for the review. Where a published report does not appear to report one of the following outcomes, we will access the trial protocol and contact the trial authors to ascertain whether the outcomes were measured but not reported. Relevant trials that measured these outcomes but did not report the data at all, or are not in a useable format, will be included in the review as part of the narrative. We will focus on short‐term outcomes in this review. 'Short‐term' is defined as outcomes measured in an ED such as 'up to 24 hours post‐VM therapy'. For outcomes that can occur more than once in a participant during follow‐up, we plan to assess the number of participants with at least one event.

Primary outcomes

  1. Reversion of SVT to sinus rhythm

  2. Hypotension

  3. Asystolic pause

 We will define return to sinus rhythm (SR) as the SR confirmed by a 12‐lead ECG after the VM in the ED.

Secondary outcomes

  1. Number of attempts of each manoeuvre

  2. Amount of adenosine

  3. Emergency antiarrhythmic treatment

  4. Increased heart rate (events of increased heart rate compared to heart rate that did not increase compared to baseline)

  5. Light‐headedness

  6. Nausea

  7. Musculoskeletal pain

  8. Transient headache

  9. Episodes of ventricular escape activity

  10. Any patient‐reported outcomes (PROMS) using a validated scale such as the 36‐item Short Form Health Survey (SF‐36) (Ware 2000), Arrhythmia‐Specific Questionnaire in Tachycardia and Arrhythmia (ASTA) (Walfridsson 2012), and Psychometric Evaluation of the Patient Perspective of Arrhythmia Questionnaire (PPAQ) (Wood 2009)

  11. Treatment cost

  12. Duration of stay in the ED

Search methods for identification of studies

Electronic searches

We will identify trials through systematic searches of the following bibliographic databases:

  • Cochrane Central Register of Controlled Trials (CENTRAL);

  • MEDLINE (Ovid, from 1946 onwards);

  • Embase (Ovid, from 1980 onwards);

  • Web of Science Core Collection (Clarivate Analytics, from 1900 onwards).

We will adapt the preliminary search strategy for MEDLINE (Ovid) (Appendix 1) for use in the other databases. We will apply the Cochrane sensitivity‐maximising RCT filter (Lefebvre 2019) to MEDLINE (Ovid) and adaptations of it to the other databases, except CENTRAL.

We will also conduct a search of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov/) and the World Health Organization International Clinical Trial Registry Platform (apps.who.int/trialsearch/) for ongoing or unpublished trials.

We will search all databases from their inception to the present, and impose no restriction on language of publication or publication status.

We will not perform a separate search for adverse effects of interventions used for the treatment of SVT. We will consider adverse effects described in the included studies only.

Searching other resources

We will check the reference lists of all included studies and any relevant systematic reviews identified for additional references to trials. We will also examine any relevant retraction statements and errata for included studies. 

Data collection and analysis

Selection of studies

Two review authors (SY and SK) will independently screen the titles and the abstracts of all the potentially eligible studies identified by the search, coding them as 'retrieve' (eligible/unclear) or 'do not retrieve'. In case of disagreement, a third review author (TT) will be asked to arbitrate. We will retrieve the full‐text study reports/publication, and two review authors (SY and SK) will independently screen the full texts and identify studies for inclusion, and identify and record reasons for exclusion of the ineligible studies. Any disagreements will be resolved through discussion or by consulting a third review author (TT) if required. We will identify and exclude duplicates and collate multiple reports of the same study so that each study, rather than each report, is the unit of interest in the review. We will record the selection process in sufficient detail to complete a PRISMA flow diagram and 'Characteristics of excluded studies' table (Liberati 2009).

Data extraction and management

We will use a data collection form for study characteristics and outcome data that has been piloted on at least one study in the review. One review author (SY) will extract study characteristics from the included studies. We will extract the following study characteristics.

  1. Method: study design, total duration of study, details of any 'run in' period, number of study centres and location, study setting, and date of study.

  2. Participants: N randomised, N lost to follow‐up/withdrawn, N analysed, mean age, age range, gender, cardiogenic shock, QRS duration, inclusion criteria, and exclusion criteria.

  3. Interventions: intervention, comparison, concomitant medications, and excluded medications.

  4. Outcomes: primary and secondary outcomes specified and collected, and time points reported.

  5. Notes: funding for trial, and notable conflicts of interest of trial authors.

The timing for extraction of outcomes will be after the VM (up to three times) in ED.

Two review authors (SY and SK) will individually extract outcome data from the included studies. Any disagreements will be resolved by consensus or by involving a third person (TT or NW). One review author (SY) will transfer data into the Review Manager 5 file (Review Manager 2014). We will double‐check that data have been entered correctly by comparing the data presented in the systematic review with the data extraction form. A second review author (SK) will spot‐check study characteristics for accuracy against the trial report.

Assessment of risk of bias in included studies

Two review authors (SY and SK) will independently assess risk of bias for each study using version 2 of the Cochrane 'Risk of bias' tool (RoB 2), outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019a). We plan to use the RoB 2 Excel tool to implement RoB 2 (available on the riskofbiasinfo.org website) to manage the assessment of bias using RoB 2. Any disagreements will be resolved by discussion or by involving another review author (NW). We will assess the risk of bias of specific trial results according to the following domains.

  1. Bias arising from the randomisation process

  2. Bias due to deviations from intended interventions

  3. Bias due to missing outcome data

  4. Bias in measurement of the outcome

  5. Bias in selection of the reported result

We will assess risk of bias for the outcomes included in the 'Summary of findings' table. We are interested in qualifying the effect of assignment to the interventions at baseline, regardless of whether the interventions were received as intended (the 'intention‐to‐treat' effect).

We will use the signalling questions in the RoB 2 tool, rating each domain as 'low risk of bias', 'some concerns', or 'high risk of bias'. We will summarise the 'Risk of bias' judgements across different studies for each of the domains listed for each outcome. The overall risk of bias for the result is the least favourable assessment across the domain of bias.

When considering treatment effects, we will take into account the risk of bias for studies that contributed to the outcome.

For cluster‐RCTs, we will use the RoB 2 tool as it is and add an additional domain specific for cluster‐RCTs from www.riskofbias.info/welcome/rob-2-0-tool/archive-rob-2-0-cluster-randomized-trials-2016. We will use the signalling questions from the archived version and the guidance in Chapter 23 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019c). For cross‐over RCTs, we will only include data from the first phase, precluding the need to use the cross‐over RCT version of RoB 2. We will use the standard version of RoB 2 as it is.

Measures of treatment effect

We will analyse dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs) and continuous data as mean difference (MD) or standardised mean difference (SMD) with 95% CIs. We will represent the MD with 95% CIs for continuous data such as treatment costs and time in ED. We will use the SMD instead of MD when there are differences in scale measurement. We will interpret the results of SMD as follows: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect (Cohen 1988).

Unit of analysis issues

The unit of analysis is the individual participant. Consultation with an appropriately qualified statistician is not required if no unit of analysis issues arise.

If we include cluster‐RCTs, we will adjust their standard errors using the intracluster correlation coefficient (ICC). We will exclude any RCTs without the ICC. We will include only the first phase of the cross‐over trials because patients with recurrent SVT often take the 'pill in the pocket' treatment using some kind of antiarrhythmic drug; although SVT can be a recurrent disease, we will exclude the effect of the 'pill in the pocket' treatment at the second phase in cross‐over trials. 

If studies with multiple treatment arms are found, we will include all intervention groups related to the review. If an RCT has two intervention groups and a single comparator group, we will divide the number of participants in the comparator group into the number of eligible intervention groups in order to avoid double‐counting of the comparator when included in the same analysis.

Dealing with missing data

We will contact the original investigators or study sponsors in order to verify key study characteristics and to obtain missing numerical outcome data where possible (e.g. when a study is identified as an abstract only). Where possible, we will use the Review Manager 5 calculator to calculate missing standard deviations using other data from the trial (Review Manager 2014), such as CIs, based on the method outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019b). Where this is not possible, and the missing data are thought to introduce serious bias, we will explore the impact of including such studies in the overall assessment of results by a sensitivity analysis. 

Assessment of heterogeneity

We will visually inspect forest plots to consider the direction and magnitude of effects and the degree of overlap between CIs. We will use the I2 statistic to measure heterogeneity amongst the trials in each analysis, but acknowledge that there is substantial uncertainty in the value of I2 when there is only a small number of studies. We will also consider the P value from the Chi2 test. If we identify substantial heterogeneity, we will report it and explore the possible cause by prespecified subgroup analysis. We will set a significance level of 0.05. The I2 statistic calculates the percentage of variability due to heterogeneity rather than chance. We will interpret the heterogeneity as follows.

  • 0 to 40%: might not be important

  • 30 to 60%: may represent moderate heterogeneity

  • 50% to 90%: may represent substantial heterogeneity

  • 75% to 100%: considerable heterogeneity

We will also calculate Tau2, the between‐study variance in a random‐effects meta‐analysis, by forest plot created in Review Manager 5 (Review Manager 2014). The Tau2 gives an indication of the spread of true intervention effects.

Assessment of reporting biases

If we are able to pool more than 10 trials, we will create and examine a funnel plot to explore possible small‐study biases for the primary outcomes. However, we will not use a funnel plot when the number of included studies is less than 10 because it has insufficient power to detect the effects of studies with small sample size.

We will also assess measurement of reporting bias 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.

Data synthesis

We will undertake meta‐analyses only where this is meaningful, that is if the treatments, participants, and the underlying clinical question are similar enough for pooling to make sense. We will use a random‐effects model because there may be heterogeneity amongst the studies, such as the type and proportion of SVT, age, and sex. When meta‐analysis is considered to be improper due to insufficient data or high level of heterogeneity, we will provide a narrative assessment of the included studies.

The primary analysis will include only studies with a low risk of bias. We will perform a sensitivity analysis to show how conclusions might be affected if studies at high risk of bias and those with some concerns are included. If there are insufficient studies with a low risk of bias to identify meaningful differences, we will include all eligible studies in the primary analysis.

Subgroup analysis and investigation of heterogeneity

We plan to carry out the following subgroup analyses for any outcomes with substantial heterogeneity.

  1. Sex

  2. Race/ethnicity

  3. Recurrent or first episode of SVT

If we are unable to obtain the subgroup information, we will not perform subgroup analysis. We will use the formal test for subgroup differences in Review Manager 5 (Review Manager 2014), and base our interpretation on this.

Sensitivity analysis

We plan to carry out the following sensitivity analyses to test whether key methodological factors or decisions have affected the main results. We will perform sensitivity analyses only if there are enough studies to identify meaningful differences. The primary sensitivity analyses will include all studies regardless of risk of bias. A secondary sensitivity analysis will compare trials that reported intention‐to‐treat data against trials that only reported complete‐case analyses. We will additionally conduct a sensitivity analysis for trials reporting dropout rates of 10% or more. 

Summary of findings and assessment of the certainty of the evidence

Two review authors (SY and SK) will independently assess the certainty of the evidence. Any disagreements will be resolved by discussion or by involving a third review author (TT). We will use methods and recommendations described in Chapter 14 of the Cochrane Handbook for Systematic Reviews of Interventions (Schünemann 2019), employing GRADEpro GDT software (GRADEpro GDT). We will use the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias). Judgements will be justified, documented, and incorporated into the reporting of results for each outcome. We will use the overall 'Risk of bias' judgement when assessing study limitations. We will justify all decisions to downgrade the certainty of evidence using footnotes, and make comments to aid the reader's understanding of the review where necessary.

We will create a 'Summary of findings' table using the following outcomes.

  • Reversion of SVT to sinus rhythm

  • Hypotension

  • Asystolic pause

  • Amount of adenosine