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Myocardial Protective Effects of Shenfu Injection after Mitral Valve Replacement Surgery; A Systematic Review and Meta Analysis

Article information

J Korean Med. 2022;43(3):164-180
Publication date (electronic) : 2022 September 1
doi : https://doi.org/10.13048/jkm.22038
Bong-Jin Shin1orcid_icon, Ji-Ho Kim1orcid_icon, Mu-Hyeok Ahn1orcid_icon, Jung-Nam Kwon1,2,orcid_icon
1Pusan National University School of Korean Medicine
2Department of Internal Medicine of Korean Medicine, Pusan University Korean Medicine Hospital
Correspondence to: Jung-Nam Kwon, School of Korean medicine, Pusan National University 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, Republic of Korea., Tel: +82-55-360-5956, Fax: +82-55-360-5509, E-mail: jnkwon@pusan.ac.kr

BJS and JHK contributed equally to the work.

Received 2022 February 11; Revised 2022 June 30; Accepted 2022 July 15.

Abstract

Objectives

The purpose of this study was to evaluate the effects of shenfu injection on myocardial protective effects after mitral valve replacement surgery.

Methods

We searched four international databases (PUBMED, Embase, Web of Science and CNKI) and three domestic electronic databases (OASIS, RISS and NDSL) for relevant studies. We used following keywords ‘shenfu’, ‘valve replacement’, ‘mitral valve’ at PUBMED, Embase and Web of Science; ‘二尖瓣’, ‘参附注射液’, ‘瓣膜’ at CNKI and ‘이첨판’, ‘판막’, ‘삼부’ at domestic databases. The search range included randomized controlled trials. When appropriate, meta-analyses were performed.

Results

Seven randomized controlled trials were selected. All studies used Shenfu injection after mitral valve replacement surgery. We analyzed myocardial damage, cardiac function, patients’ recovery rate, with various evaluation indicators. We also used meta-analysis for CK-MB, cTnI, MDA and voluntary recovery of heartbeat. CK-MB was analyzed in two subgroups: 8 hours and 24 hours after surgery. Std was −2.34(95% CI −4.10, −0.58) for 8 hours and −1.95(95% CI −4.79 to 0.88) for 24 hours. 8 hours showed statistically significant difference. cTnI appeared significant decrease with Std of −2.13(95% CI −2.60, −1.66). MDA showed significant decrease with Std of −0.95(95% CI −1.43 to −0.47). Voluntary recovery of heartbeat significantly increased with the odd ratio of 4.34(95% CI 1.76, 10.70).

Conclusions

We suggest that Shenfu injection after Mitral valve replacement surgery may have significant myocardial protective effects in terms of reducing myocardial damages, reactive oxygen species, increasing cardiac function and patients’ recovery after surgery. However, the evidence is limited, further research is required.

Keywords: Mitral valve replacement; Myocardial protection; Shenfu injection
Fig 1

PRISMA flow chart.

Fig 2

The meta results of CK-MB in 8 hours (SFI vs Control goup).

Fig 3

The meta results of CK-MB in 24 hours (SFI vs Control goup).

Fig 4

The meta results of cTnI in 8 hours (SFI vs Control goup).

Fig 5

The meta results of MDA in 24 hours (SFI vs Control goup). (502)

Fig 6

The meta results of Voluntary recovery of heartbeat (SFI vs Control goup).

Fig 7

Risk of bias summary.

Fig 8

Risk of bias graph.

Characteristics of Selected studies

Characteristics of Selected studies

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Article information Continued

Fig 1

Fig 1

PRISMA flow chart.

Fig 2

Fig 2

The meta results of CK-MB in 8 hours (SFI vs Control goup).

Fig 3

Fig 3

The meta results of CK-MB in 24 hours (SFI vs Control goup).

Fig 4

Fig 4

The meta results of cTnI in 8 hours (SFI vs Control goup).

Fig 5

Fig 5

The meta results of MDA in 24 hours (SFI vs Control goup). (502)

Fig 6

Fig 6

The meta results of Voluntary recovery of heartbeat (SFI vs Control goup).

Fig 7

Fig 7

Risk of bias summary.

Fig 8

Fig 8

Risk of bias graph.

Table 1

Characteristics of Selected studies

First author (year) Subject size (n) NYHA Class II: Class III (n : n) Male : Female (n : n) Age (M±SD) Criteria
Inclusion criteria Exclusion criteria
Qing yong (2006)16) E 20 15:5 8:12 39.0±10.4 Patients undergoing mitral valve replacement with cardiopulmonary bypass Not mentioned
C 20 13:7 9:11 37.0±9.3
Li kai (2009)17) E 20 17:3 10:10 66.8±5.6 Patients undergoing mitral valve replacement surgery Not mentioned
C 20 15:5 7:13 65.6±5.1
Zhen Chuandong (2009)18) E 10 All patients are NYHA Class II or III Not mentioned Not mentioned Patients undergoing mitral valve replacement with cardiopulmonary bypass Not mentioned
C 10
Wang Fangjun (2010)19) E 30 All patients are NYHA Class II or III 13:17 34.5±6.1 Patients undergoing mitral valve replacement with cardiopulmonary bypass Not mentioned
C 30 14:16 36.5±5.7
Wu Jun (2018)20) E 8 6:2 4:4 46.4±6.3 Patients undergoing mitral valve replacement surgery Not mentioned
C 8 6:2 3:5 46.1±6.1
Song Zhi-bin (2020)21) E 39 20:19 26:13 67.37±12.68

  1. Patients with NYHA Grade 2, 3

  2. Patients with severe mitral stenosis by pulsation treatment echocardiography (<1.5cm2)

  1. Need of aortic balloon reverse

  2. Treated with antiplatelet drugs, anticoagulants or other drugs within 1 week before the study

  3. Patients with severe vascular disease

  4. Patients with severe coagulopathy and immunodeficiency

  5. Complications of liver and kidney dysfunction

  6. Patients with infections and malignancies.
C 39 18:21 23:16 66.91±13.04
Feng Yi (2020)22) E 30 Not mentioned 54:66 62.19±0.28 Patients undergoing mitral valve replacement with cardiopulmonary bypass Not mentioned
C 30

C: Control group, E: Experimental group, M: Mean, SD: Standard Deviation SFI : Shenfu Injection

*

Specific number of patients was not mentioned in both groups.

Table 2

Characteristics of Selected studies

First author (year) Interventions Results /Time of examination & Results Adverse events
Qing yong (2006)16) E 1.0 mL/kg SFI* was injected before the surgery, after induction of anesthesia, 12hours, 36hours, and 60hours after surgery, respectively.

  1. CK (10^4U/L)

  2. HR (beats/min) / T2†, T3†

  3. MAP (mmHg) / T2†, T3†

  1. CK-MB (ug/L) / T1†, T8†, T10†, T11†,T12†, T13†

  2. The amount of dopamine used. [mg/kg] / T15†

  3. The amount of amrinone used. [mg/kg] / T15†

 Not mentioned
C 250 mL saline was injected before the surgery, after induction of anesthesia, 12 hours, 36 hours, and 60 hours after surgery, respectively. Not mentioned
Li kai (2009)17) E 1.5 mL/kg SFI was transfused through central vein before operations and pumped via CPB, respectively.

  1. HR (beats/min)

  2. MAP (mmHg)

  3. PAWP (mmHg)

  4. CI, SVI, LVSWI (kg*min)

  5. CK-MB (U/L)

  1. cTnI (ng/mL)

  2. MYO (ng/mL)

  3. MDA (nmol/mL)

  4. Voluntary recovery of heartbeat (%)

  5. The amount of dopamine used. [mg/(kg*min)]

 Not mentioned
C No additional treatment. Not mentioned
Zhen Chuandong (2009)18) E 1.5 mL/kg SFI was injected in pre-filling via CPB.

  1. Detached from ventilator (h)

  2. Duration of ICU (h)

  3. VAFS

  1. Hospitalization period after surgery (d) / T16†

  2. MDA (nmol/mL) / T4†, T9†,

  3. SOD (nU/mL) / T4†, T9†, T11†

 Not mentioned
C No additional treatment. Not mentioned
Wang Fangjun (2010)19) E 1 mL/kg SFI was injected 60sec before unclamping aorta via CPB.

  1. Voluntary recovery of heartbeat (%)

  2. ST change from aortic opening to heart rate†

  3. ST segment normalization time†

  1. Parallel cycle time

  2. The amount of dopamine used [mg/kg] / T5†, T6†, T7†, T15†

  3. Ventricular fibrillation rate†

 Not mentioned
C 1 mL/kg saline was injected 60sec before unclamping aorta via CPB. Not mentioned
Wu Jun (2018)20) E 1.5 mL/kg SFI was transfused through central vein before operations and pumped via CPB, respectively, as soon as clamped aorta was unclamped.

  1. CKMB (U/L)

  2. cTnI (ng/mL)

  3. MDA (nmol/mL)

  1. Voluntary recovery of heartbeat (%)

  2. The amount of dopamine used. [mg/(kg*min)]

 Not mentioned
C No additional treatment. Not mentioned
Song Zhi-bin (2020)21) E 5.0 mL/kg SFI was injected intravenously with 250mL of 5% glucose solution

  1. Urine discharge 24 hours after surgery (mL/h)

  2. Duration of ICU (h) / T16†

  3. Detached from ventilator (h) / T16†

  4. sICAM-1(pg/mL) / T14†

  1. cTnI (μg /L) / T14†

  2. CKMB (μg /L) / T14†

  3. LVEF (%)/ T14†

 Nausea 2
Dizziness and headache 12
Tachycardia 1
C Same amount of saline as Group E. Headache 1
Weakness 1
Tachycardia 1
Feng Yi (2020)22) E 1.5 mL/kg SFI was injected during prefilling and opening of the aorta via CPB

  1. cTnI (ng/mL) / T10†

  2. CKMB (U/L) / T10†

 Not mentioned
C No additional treatment. Not mentioned
*

SFI:Shenfu injection,

†

p<0.05

††

p<0.01

C: Control group, CI: Cardiac index, CK:Creatine kinase, CK-MB: Creatine kinase MB Fraction, CPB:Cardiopulmonary bypass, cTnI: Cardiac troponin, DBP: Diastolic Blood Pressure, E: Experimental group HR: Heart rate, ICU: Intensive care unit, IPC:Ischemic preconditioning, LVEF: Left ventricular ejection fraction, LVSWI:Left ventricular stroke work index, MAP: Mean arterial pressure, MDA: Malondia ldehyde, MYO: Myogloblin, PAWP: Pulmonary capillary wedge pressure, SBP: Systolic Blood Pressure, :sICAM-1: Soluble intercelluelar adhesion molecule-1, SOD: Superoxide dismutase, SpO2:Saturation of percutaneous oxygen, SVI: Stroke volume index, VAFS:Visual analog Fatigue Scale

T1: Before operation or clamping aorta or anesthesia. T2 : Before ascending aorta occlusion.T3 : 30minutes after heart beat. T4: Immediately after operation. T5: Up to 30minutes after surgery. T6: 1 hour after the opening of the ascending aorta or 30minutes to 1hour after surgery. T7: 1 hour to 90minutes after surgery. T8: 2 hours after operation or opening of the ascending aorta T9: 3 hours after operation. T10 : 8hours after operation or opening of the ascending aorta T11 : 24hours after operation or opening of the ascending aorta T12 : 48hours after operation T13 : 3days after operation T14: 4days after operation T15 : During the period of residence in ICU T16 : After surgery