Neuromuscular electrical stimulation for the prevention of venous thromboembolism

Shahab Hajibandeh; Shahin Hajibandeh; George A Antoniou; James RH Scurr; Francesco Torella

doi:10.1002/14651858.CD011764.pub2

静脈血栓塞栓症予防に対する神経筋電気刺激

Appendices

Appendix 1. Glossary of terms for lay readers

Terms	Meaning
Anticoagulant	Having the effect of retarding or inhibiting the coagulation or clotting of blood. Anticoagulants are a class of drugs that work to prevent coagulation of blood.
Compliance	The action or fact of complying with treatment
Deep vein thrombosis (DVT)	Formation of a blood clot in a deep vein ‐ usually in the leg or pelvic veins
Endothelium	The tissue that forms a single layer of cells lining various organs and cavities of the body, especially the blood vessels, heart, and lymphatic vessels
Factor V Leiden	A mutation of one of the clotting factors in the blood called factor V. This mutation can increase the chance of developing abnormal blood clots (thrombophilia), usually in the veins.
Graduated compression stockings (GCS)	Elastic garments worn around the leg, compressing the limb. They help to prevent the occurrence or further progression of venous disorders such as oedema, phlebitis, and thrombosis.
Hypercoagulable state	An abnormality of blood coagulation that increases the risk of thrombosis
Incidence	The occurrence, rate, or frequency of a disease
Intermittent pneumatic compression devices (IPCD)	A therapeutic technique used in medical devices that include an air pump and inflatable auxiliary sleeves, gloves, or boots in a system designed to improve venous circulation in the limbs of patients who suffer oedema or risk of DVT or PE
Malignancy	The state or presence of a malignant tumour; cancer
Morbidity	The frequency of complications resulting from treatment or disease
Mortality	The frequency of death resulting from treatment or disease
Neuromuscular electrical stimulation (NMES)	Delivery of electrical impulses via electrodes to the skin over selected muscle groups or nerves to induce an involuntary muscle contraction
Oedema	Fluid retention in the body
Paraplagia	Paralysis of the legs and lower body, typically caused by spinal injury or disease
Pathogenesis	The manner of development of a disease
Pharmacology	The science of drugs including their origin, composition, pharmacokinetics, therapeutic use, and toxicology
Prophylaxis	Treatment given or action taken to prevent disease
Pulmonary embolism (PE)	A sudden blockage in a lung artery that is caused by a blood clot that travels to the lung from a vein in the leg
Subcutaneous	Situated or applied under the skin
Thrombophilia	An abnormal tendency to develop blood clots
Thrombosis	Blood clots in blood vessels
Venous thromboembolism	The occurrence DVT or PE or both

Appendix 2. CENTRAL search strategy

#1	MESH DESCRIPTOR Electric Stimulation EXPLODE ALL TREES	1788
#2	(neuromusc* near3 stimul*):TI,AB,KY	495
#3	(electr* near3 stimul*):TI,AB,KY	7108
#4	(musc* near3 stimul*):TI,AB,KY	711
#5	(calf* near3 stimul*):TI,AB,KY	18
#6	(foot* near3 stimul*):TI,AB,KY	47
#7	(lower near3 stimul*):TI,AB,KY	168
#8	(limb near3 stimul*):TI,AB,KY	52
#9	(peroneal near3 stimul*):TI,AB,KY	37
#10	electromyostimul*:TI,AB,KY	66
#11	NMES:TI,AB,KY	242
#12	geko*:TI,AB,KY	8
#13	#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12	7873
#14	MESH DESCRIPTOR Thrombosis	1267
#15	MESH DESCRIPTOR Thromboembolism	921
#16	MESH DESCRIPTOR Venous Thromboembolism	258
#17	MESH DESCRIPTOR Venous Thrombosis EXPLODE ALL TREES	2041
#18	(thrombus* or thrombopro* or thrombotic* or thrombolic* or thromboemboli* or thrombos* or embol*):TI,AB,KY	18996
#19	MESH DESCRIPTOR Pulmonary Embolism EXPLODE ALL TREES	748
#20	(PE or DVT or VTE):TI,AB,KY	4988
#21	((vein* or ven) near thromb):TI,AB,KY	6717
#22	(blood near3 clot*):TI,AB,KY	2966
#23	(pulmonary near3 clot*):TI,AB,KY	5
#24	(lung near3 clot*):TI,AB,KY	4
#25	(venous near3 stasis):TI,AB,KY	128
#26	(venous near3 empty*):TI,AB,KY	10
#27	(blood near3 stasis):TI,AB,KY	453
#28	(blood near3 supply):TI,AB,KY	7412
#29	MESH DESCRIPTOR Hemodynamics EXPLODE ALL TREES	46548
#30	MESH DESCRIPTOR Lower Extremity EXPLODE ALL TREES WITH QUALIFIERS BS	1521
#31	(blood near3 flow):TI,AB,KY	12698
#32	hemodynamic*:TI,AB,KY	21594
#33	haemodynamic*:TI,AB,KY	5411
#34	fibrinoly*:TI,AB,KY	4822
#35	#14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #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	93374
#36	#13 AND #35	709

Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 4

Forest plot of comparison: 1 NMES versus alternative prophylaxis, outcome: 1.1 Total DVT.

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Figure 5

Forest plot of comparison: 2 NMES versus no prophylaxis, outcome: 2.1 Total DVT.

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Analysis 1.1

Comparison 1 NMES versus alternative prophylaxis, Outcome 1 Total DVT.

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Analysis 1.2

Comparison 1 NMES versus alternative prophylaxis, Outcome 2 Asymptomatic DVT.

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Analysis 1.3

Comparison 1 NMES versus alternative prophylaxis, Outcome 3 Symptomatic DVT.

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Analysis 1.4

Comparison 1 NMES versus alternative prophylaxis, Outcome 4 PE.

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Analysis 1.5

Comparison 1 NMES versus alternative prophylaxis, Outcome 5 Total VTE.

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Analysis 2.1

Comparison 2 NMES versus no prophylaxis, Outcome 1 Total DVT.

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Analysis 2.2

Comparison 2 NMES versus no prophylaxis, Outcome 2 Asymptomatic DVT.

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Analysis 2.3

Comparison 2 NMES versus no prophylaxis, Outcome 3 Symptomatic DVT.

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Analysis 2.4

Comparison 2 NMES versus no prophylaxis, Outcome 4 PE.

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Analysis 2.5

Comparison 2 NMES versus no prophylaxis, Outcome 5 Total VTE.

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Analysis 3.1

Comparison 3 NMES versus low‐dose heparin, Outcome 1 Total DVT.

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Analysis 3.2

Comparison 3 NMES versus low‐dose heparin, Outcome 2 Asymptomatic DVT.

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Analysis 3.3

Comparison 3 NMES versus low‐dose heparin, Outcome 3 Symptomatic DVT.

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Analysis 4.1

Comparison 4 NMES versus Dextran 40, Outcome 1 Total DVT.

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Analysis 4.2

Comparison 4 NMES versus Dextran 40, Outcome 2 PE.

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Analysis 4.3

Comparison 4 NMES versus Dextran 40, Outcome 3 Total VTE.

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Analysis 5.1

Comparison 5 Combined NMES and low‐dose heparin versus no prophylaxis, Outcome 1 Total DVT.

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Analysis 6.1

Comparison 6 Combined NMES and low‐dose heparin versus low‐dose heparin, Outcome 1 Total DVT.

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Analysis 7.1

Comparison 7 NMES versus GCS, Outcome 1 Total DVT.

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Analysis 7.2

Comparison 7 NMES versus GCS, Outcome 2 PE.

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Analysis 8.1

Comparison 8 NMES versus IPCD, Outcome 1 Total DVT.

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Analysis 8.2

Comparison 8 NMES versus IPCD, Outcome 2 PE.

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Summary of findings for the main comparison. NMES compared to alternative prophylaxis for the prevention of venous thromboembolism

NMES compared to alternative prophylaxis for the prevention of venous thromboembolism
Patient or population: participants at risk of venous thromboembolism Setting: hospital, secondary care Intervention: NMES Comparison: alternative prophylaxis
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with alternative prophylaxis	Risk with NMES
Total DVT Follow‐up: mean 11 days	Study population		OR 1.01 (0.60 to 1.70)	415 (6 RCTs)	⊕⊕⊝⊝ LOW^a,b
	170 per 1000	172 per 1000 (110 to 259)
Asymptomatic DVT Follow‐up: 8 days	Study population		OR 1.61 (0.40 to 6.43)	89 (1 RCT)	⊕⊕⊝⊝ LOW^a,c
	82 per 1000	125 per 1000 (34 to 364)
Symptomatic DVT Follow‐up: 8 days	Study population		OR 0.40 (0.02 to 10.07)	89 (1 RCT)	⊕⊕⊝⊝ LOW^a,c
	20 per 1000	8 per 1000 (0 to 173)
PE Follow‐up: mean 4 days	Study population		OR 1.31 (0.38 to 4.48)	126 (2 RCTs)	⊕⊕⊝⊝ LOW^a,c
	70 per 1000	90 per 1000 (28 to 253)
Total VTE Follow‐up: 6 days	Study population		OR 0.92 (0.34 to 2.52)	72 (1 RCT)	⊕⊕⊝⊝ LOW^a,c
	314 per 1000	297 per 1000 (135 to 536)
Bleeding (major and minor)	see comment	see comment	not estimable	415 (6 RCTs)	‐	None of the studies in this comparison reported this outcome.
Assumed control intervention risks were calculated by the mean number of events in control groups of selected studies for each outcome. The risk in the intervention group* (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; NMES: neuromuscular electrical stimulation; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aHigh or unclear risk of selection bias, performance bias, and detection bias ‐ downgraded by one level. ^bModerate level of between‐study heterogeneity ‐ downgraded by one level. ^cFew participants and few events and thus wide confidence intervals ‐ downgraded by one level.

Summary of findings for the main comparison. NMES compared to alternative prophylaxis for the prevention of venous thromboembolism

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Summary of findings 2. NMES compared to no prophylaxis for prevention of venous thromboembolism

NMES compared to no prophylaxis for prevention of venous thromboembolism
Patient or population: participants at risk of venous thromboembolism Setting: hospital, secondary care Intervention: NMES Comparison: no prophylaxis
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with no prophylaxis	Risk with NMES
Total DVT Follow‐up: mean 7 days	Study population		OR 0.40 (0.23 to 0.70)	576 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a
	219 per 1000	101 per 1000 (61 to 164)
Asymptomatic DVT Follow‐up: 7 days	Study population		OR 0.32 (0.06 to 1.62)	200 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	60 per 1000	20 per 1000 (4 to 94)
Symptomatic DVT Follow‐up: 7 days	Study population		OR 0.06 (0.00 to 1.36)	160 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	50 per 1000	3 per 1000 (0 to 67)
PE Follow‐up: 6 days	Study population		OR 0.36 (0.12 to 1.07)	77 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	350 per 1000	162 per 1000 (61 to 366)
Total VTE Follow‐up: 6 days	Study population		OR 0.23 (0.09 to 0.59)	77 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	650 per 1000	299 per 1000 (143 to 523)
Bleeding (major and minor)	see comment	see comment	not estimable	576 (4 RCTs)	‐	None of the studies in this comparison reported this outcome.
Assumed control intervention risks were calculated by the mean number of events in control groups of selected studies for each outcome. The risk in the intervention group* (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; NMES: neuromuscular electrical stimulation; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aHigh or unclear risk of selection bias, performance bias, and detection bias ‐ downgraded by one level. ^bFew participants and few events and thus wide confidence intervals ‐ downgraded by one level.

Summary of findings 2. NMES compared to no prophylaxis for prevention of venous thromboembolism

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Summary of findings 3. NMES compared to low‐dose heparin for the prevention of venous thromboembolism

NMES compared to low‐dose heparin for the prevention of venous thromboembolism
Patient or population: participants at risk of venous thromboembolism Setting: hospital, secondary care Intervention: NMES Comparison: low‐dose heparin
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with low‐dose heparin	Risk with NMES
Total DVT Follow‐up: mean 7 days	Study population		OR 2.78 (1.19 to 6.48)	194 (2 RCTs)	⊕⊕⊝⊝ LOW^a,b
	87 per 1000	208 per 1000 (101 to 380)
Asymptomatic DVT Follow‐up: 8 days	Study population		OR 1.61 (0.40 to 6.43)	89 (1 RCT)	⊕⊕⊝⊝ LOW^b,c
	82 per 1000	125 per 1000 (34 to 364)
Symptomatic DVT Follow‐up: 8 days	Study population		OR 0.40 (0.02 to 10.07)	89 (1 RCT)	⊕⊕⊝⊝ LOW^b,c
	20 per 1000	8 per 1000 (0 to 173)
PE	see comment	see comment	not estimable	194 (2 RCTs)	‐	None of the studies in this comparison reported this outcome.
Total VTE	see comment	see comment	not estimable	194 (2 RCTs)	‐	None of the studies in this comparison reported this outcome.
Bleeding (major and minor)	see comment	see comment	not estimable	194 (2 RCTs)	‐	None of the studies in this comparison reported this outcome.
Assumed control intervention risks were calculated by the mean number of events in control groups of selected studies for each outcome. The risk in the intervention group* (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; NMES: neuromuscular electrical stimulation; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aHigh or unclear risk of selection bias, performance bias, and detection bias ‐ downgraded by one level. ^bFew participants and few events and thus wide confidence intervals ‐ downgraded by one level. ^cHigh or unclear risk of selection bias and detection bias ‐ downgraded by one level.

Summary of findings 3. NMES compared to low‐dose heparin for the prevention of venous thromboembolism

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Summary of findings 4. NMES compared to Dextran 40 for the prevention of venous thromboembolism

NMES compared to Dextran 40 for the prevention of venous thromboembolism
Patient or population: participants at risk of venous thromboembolism Setting: hospital, secondary care Intervention: NMES Comparison: Dextran 40
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with Dextran 40	Risk with NMES
Total DVT Follow‐up: 6 days	Study population		OR 0.63 (0.18 to 2.19)	72 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	200 per 1000	136 per 1000 (43 to 354)
Asymptomatic DVT	see comment	see comment	not estimable	72 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Symptomatic DVT	see comment	see comment	not estimable	72 (1 RCT)	‐	The single study in this comparison did not report this outcome.
PE Follow‐up: 6 days	Study population		OR 1.50 (0.39 to 5.84)	72 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	114 per 1000	162 per 1000 (48 to 430)
Total VTE Follow‐up: 6 days	Study population		OR 0.92 (0.34 to 2.52)	72 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	314 per 1000	297 per 1000 (135 to 536)
Bleeding (major and minor)	see comment	see comment	not estimable	72 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Assumed control intervention risks were calculated by the mean number of events in control groups of selected studies for each outcome. The risk in the intervention group* (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; NMES: neuromuscular electrical stimulation; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect,
^aHigh or unclear risk of selection bias, performance bias, and detection bias ‐ downgraded by one level. ^bSingle study, few participants, and few events and thus wide confidence intervals ‐ downgraded by one level.

Summary of findings 4. NMES compared to Dextran 40 for the prevention of venous thromboembolism

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Summary of findings 5. Combined NMES and low‐dose heparin compared to no prophylaxis for the prevention of venous thromboembolism

Combined NMES and low‐dose heparin compared to no prophylaxis for the prevention of venous thromboembolism
Patient or population: participants at risk of venous thromboembolism Setting: hospital, secondary care Intervention: combined NMES and low‐dose heparin Comparison: no prophylaxis
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with no prophylaxis	Risk with combined NMES and low‐dose heparin
Total DVT Follow‐up: 28 days	Study population		OR 0.08 (0.01 to 0.76)	32 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	471 per 1000	66 per 1000 (9 to 403)
Asymptomatic DVT	see comment	see comment	not estimable	32 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Symptomatic DVT	see comment	see comment	not estimable	32 (1 RCT)	‐	The single study in this comparison did not report this outcome.
PE	see comment	see comment	not estimable	32 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Total VTE	see comment	see comment	not estimable	32 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Bleeding (major and minor)	see comment	see comment	not estimable	32 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Assumed control intervention risks were calculated by the mean number of events in control groups of selected studies for each outcome. The risk in the intervention group* (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; NMES: neuromuscular electrical stimulation; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aHigh or unclear risk of selection bias and detection bias ‐ downgraded by one level. ^bSingle study, few participants, and few events and thus wide confidence intervals ‐ downgraded by one level.

Summary of findings 5. Combined NMES and low‐dose heparin compared to no prophylaxis for the prevention of venous thromboembolism

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Summary of findings 6. Combined NMES and low‐dose heparin compared to low‐dose heparin for the prevention of venous thromboembolism

Combined NMES and low‐dose heparin compared to low‐dose heparin for the prevention of venous thromboembolism
Patient or population: participants at risk of venous thromboembolism Setting: hospital, secondary care Intervention: combined NMES and low‐dose heparin Comparison: low‐dose heparin
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with low‐dose heparin	Risk with combined NMES and low‐dose heparin
Total DVT Follow‐up: 28 days	Study population		OR 0.07 (0.01 to 0.68)	31 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	500 per 1000	65 per 1000 (10 to 405)
Asymptomatic DVT	see comment	see comment	not estimable	31 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Symptomatic DVT	see comment	see comment	not estimable	31 (1 RCT)	‐	The single study in this comparison did not report this outcome.
PE	see comment	see comment	not estimable	31 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Total VTE	see comment	see comment	not estimable	31 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Bleeding (major and minor)	see comment	see comment	not estimable	31 (1 RCT)	‐	The single study in this comparison did not report this outcome.
Assumed control intervention risks were calculated by the mean number of events in control groups of selected studies for each outcome. The risk in the intervention group* (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; NMES: neuromuscular electrical stimulation; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aHigh or unclear risk of selection bias and detection bias ‐ downgraded by one level. ^bSingle study, few participants, and few events and thus wide confidence intervals ‐ downgraded by one level.

Summary of findings 6. Combined NMES and low‐dose heparin compared to low‐dose heparin for the prevention of venous thromboembolism

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Summary of findings 7. NMES compared to GCS for the prevention of venous thromboembolism

NMES compared to GCS for the prevention of venous thromboembolism
Patient or population: participants at risk of venous thromboembolism Setting: hospital, secondary care Intervention: NMES Comparison: GCS
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with GCS	Risk with NMES
Total DVT Follow‐up: 1 day	Study population		OR 0.32 (0.01 to 8.27)	36 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	56 per 1000	18 per 1000 (1 to 327)
Asymptomatic DVT	see comment	see comment	not estimable	36 (1 RCT)	‐	None of the studies in this comparison reported this outcome.
Symptomatic DVT	see comment	see comment	not estimable	36 (1 RCT)	‐	None of the studies in this comparison reported this outcome.
PE Follow‐up: 1 day	Study population		OR 0.32 (0.01 to 8.27)	36 (1 RCT)	⊕⊕⊝⊝ LOW^a,b
	56 per 1000	18 per 1000 (1 to 327)
Total VTE	see comment	see comment	not estimable	36 (1 RCT)	‐	None of the studies in this comparison reported this outcome.
Bleeding (major and minor)	see comment	see comment	not estimable	36 (1 RCT)	‐	None of the studies in this comparison reported this outcome.
Assumed control intervention risks were calculated by the mean number of events in control groups of selected studies for each outcome. The risk in the intervention group* (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; GCS: graduated compression stockings; NMES: neuromuscular electrical stimulation; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aHigh or unclear risk of selection bias, performance bias, and detection bias ‐ downgraded by one level. ^bSingle study, few participants, and few events and thus wide confidence intervals ‐ downgraded by one level.

Summary of findings 7. NMES compared to GCS for the prevention of venous thromboembolism

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Summary of findings 8. NMES compared to IPCD for the prevention of venous thromboembolism

NMES compared to IPCD for the prevention of venous thromboembolism
Patient or population: participants at risk of venous thromboembolism Setting: hospital, secondary care Intervention: NMES Comparison: IPCD
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with IPCD	Risk with NMES
Total DVT Follow‐up: 1 day	Study population		not estimable	36 (1 RCT)	⊕⊕⊝⊝ LOW^a,b	No DVT events were recorded.
	see comment	see comment
Asymptomatic DVT	see comment	see comment	not estimable	36 (1 RCT)	‐	None of the studies in this comparison reported this outcome.
Symptomatic DVT	see comment	see comment	not estimable	36 (1 RCT)	‐	None of the studies in this comparison reported this outcome.
PE Follow‐up: 1 day	Study population		not estimable	36 (1 RCT)	⊕⊕⊝⊝ LOW^a,b	No PE events were recorded.
	see comment	see comment
Total VTE	see comment	see comment	not estimable	36 (1 RCT)	‐	None of the studies in this comparison reported this outcome.
Bleeding (major and minor)	see comment	see comment	not estimable	36 (1 RCT)	‐	None of the studies in this comparison reported this outcome.
Assumed control intervention risks were calculated by the mean number of events in control groups of selected studies for each outcome. The risk in the intervention group* (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; DVT: deep vein thrombosis; IPCD: intermittent pneumatic compression devices; NMES: neuromuscular electrical stimulation; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism.
GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aHigh or unclear risk of selection bias, performance bias, and detection bias ‐ downgraded by one level. ^bSingle study, few participants, and few events ‐ downgraded by one level.

Summary of findings 8. NMES compared to IPCD for the prevention of venous thromboembolism

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Table 1. Neuromuscular electrical stimulation delivery in the included studies

Study	Device	Frequency (Hz)	Pulse width	Charge (mA)	Voltage (V)	Duration
Hou 2013	G6805‐II	30‐100	NR	NR	6‐15	7 days (20 minutes twice/d)
Goyal 2012	VEINOPLUS	NR	NR	NR	15–25	Only during surgery
Velmahos 2005	Lymphavision	1.75	3 ms	NR	0‐120	7‐14 days (30 minutes twice/d)
Kiudelis 2002	Mioritm 021	NR	NR	50‐100	NR	Only during surgery
Merli 1988	NR	10	50 μs	NR	NR	28 days (23 hours/d)
Bostrom 1986	NR	8	50 ms	40‐50	NR	7 days
Lindstrom 1982	NR	8	50 ms	40‐50	NR	Only during surgery
Rosenberg 1975	Thrombophylactor	NR	50 ms	NR	Adjustable	Only during surgery
NR: rot reported.

Table 1. Neuromuscular electrical stimulation delivery in the included studies

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Comparison 1. NMES versus alternative prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total DVT Show forest plot	6	415	Odds Ratio (M‐H, Fixed, 95% CI)	1.01 [0.60, 1.70]

2 Asymptomatic DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Symptomatic DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 PE Show forest plot	2	126	Odds Ratio (M‐H, Fixed, 95% CI)	1.31 [0.38, 4.48]

5 Total VTE Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 1. NMES versus alternative prophylaxis

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Comparison 2. NMES versus no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total DVT Show forest plot	4	576	Odds Ratio (M‐H, Fixed, 95% CI)	0.40 [0.23, 0.70]

2 Asymptomatic DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Symptomatic DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 PE Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5 Total VTE Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. NMES versus no prophylaxis

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Comparison 3. NMES versus low‐dose heparin

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total DVT Show forest plot	2	194	Odds Ratio (M‐H, Fixed, 95% CI)	2.78 [1.19, 6.48]

2 Asymptomatic DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Symptomatic DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 3. NMES versus low‐dose heparin

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Comparison 4. NMES versus Dextran 40

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 PE Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Total VTE Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 4. NMES versus Dextran 40

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Comparison 5. Combined NMES and low‐dose heparin versus no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 5. Combined NMES and low‐dose heparin versus no prophylaxis

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Comparison 6. Combined NMES and low‐dose heparin versus low‐dose heparin

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 6. Combined NMES and low‐dose heparin versus low‐dose heparin

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Comparison 7. NMES versus GCS

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 PE Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 7. NMES versus GCS

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Comparison 8. NMES versus IPCD

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 PE Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 8. NMES versus IPCD

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Appendix 2. CENTRAL search strategy

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Appendices

Appendix 1. Glossary of terms for lay readers

Appendix 2. CENTRAL search strategy

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