Clinical Outcomes of Angiotensin II Therapy in Vasoplegic Shock: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Selection and Data Extraction
2.2. Outcomes
2.3. Assessment of Quality and Risk of Bias
2.4. Data Analysis
3. Results
3.1. Included Studies
Author, Year | Design, Country, Follow-Up | Population (Inclusion Criteria) | Intervention and Control | Age (Years) | Gender (Male) | Primary Outcome | Background Vasopressor | Shock Cause | Outcomes |
---|---|---|---|---|---|---|---|---|---|
Khanna et al., 2017 [9] | RCT in 9 countries (USA, Australasia, and Europe) Follow-up: 28 days |
| Ang II (n = 163) vs. saline placebo (n = 158) | Ang II: 63 (52–75) * Placebo: 65 (53–75) * | Ang II: 56% Placebo: 65% | MAP response at 3 h defined as increase from baseline 10 mmHg or increase to 75 mmHg, without increase in background vasopressor dose | NE equivalent dose: * Ang II: 0.33 (0.23–0.56) mcg/kg/min Placebo: 0.34 (0.23–0.56) mcg/kg/min | Ang II: Sepsis: 78% Postoperative vasoplegia: 6% Multifactorial: 4% Other, potentially sepsis: 12% Placebo: Sepsis: 84% Postoperative vasoplegia: 6% Multifactorial: 3% Other, potentially sepsis: 7% Pancreatitis: 1% | In-Hospital mortality: 46% vs. 54%; HR 0.78 (0.57–1.07); p-value 0.12 MAP change at 3 h: 67% vs. 23%; OR 7.95 (4.76–13.3); p-value < 0.001 Multiorgan failure: 15.3% vs. 14.6% AF: 3.1% vs. 3.2% |
Wieruszewski et al., 2021 [17] | Retrospective study (5 centers), USA) Follow-up: 30 days |
| Ang II (n = 270) Then characteristics of responders (n = 180) and non-responders (n = 89) were compared | Responders: 61 ± 14 Non-responders: 57 ± 17 | Responders: 68% Non-responders: 62% | Responsiveness to ang II defined as attainment of MAP > 65 mm Hg with a stable or reduced total vasopressor dosage within 3 h | NE equivalent-dose: Responders: 0.57 ± 0.33 mcg/kg/min Non-responders: 0.55 ± 0.35 mcg/kg/min | Responders: Sepsis: 57% Postoperative vasoplegia: 10% Hemorhagic: 4% Obstructive: 2% Multifactorial 27% Non-responders: Sepsis: 52% Postoperative vasoplegia: 11% Hemorhagic: 5% Obstructive: 5% Multifactorial 28% | Responsiveness to ang II: 67% In-hospital mortality: Responsiveness to ang II was associated with reduced mortality: HR: 0.50; 95% CI, 0.35–0.71; p < 0.001 |
Klijian et al., 2021 [15] | Post hoc analysis of ATHOS-3 Follow-up: 28 days |
| Ang II (n = 9) vs. Placebo (n = 7) | Ang II: <65 y: 5 (55.6) >65 y: 4 (44.4) Placebo: <65 y: 2 (28.6) >65 y: 5 (71.4) | Ang II: 88% Placebo: 71% | MAP response at 3 h defined as increase from baseline 10 mmHg or increase to 75 mmHg, without increase in background vasopressor dose | NE equivalent dose: * Ang II: 0.28 (0.20–0.47) Placebo: 0.29 (0.23–0.40) | Vasoplegia after cardiac surgery: 100% | MAP change at 3 h: 88.9% vs. 0; p = 0.0021 In-hospital mortality: 11% vs. 14%; p-value > 0.05 |
Smith et al., 2022 [20] | Retrospective study (5 centers), USA Follow-up: 28 days |
| Ang II (n = 162) ** | 63 (51–71) * | 58.6% | MAP and norepinephrine equivalent dose difference between hour 0 and hour 3 of post-ang II | Baseline NE-equivalent dose: * 0.55 (0.38–0.82) | Septic shock: 72.2% Cardiogenic shock: 21% Non-septic distributive shock: 14.2% Hypovolemic shock: 3.1% | MAP change at 3 h: * 62 (57–70) vs. 73 (65–79); difference 9.3 (6.4–12.1); p-value < 0.001 NE equivalent dose change at 3 h: * 0.55 (0.38–0.82) vs. 0.39 (0.16–0.64); difference 0.16 (0.10–0.22); p-value < 0.001 |
Zangrillo et al., 2020 [21] | Retrospective study (1 center), Italy Follow-up: 48 h |
| Ang II: 14 ** ¶ | 64 (54–69) * | 73.3% | Change in oxygenation parameters and MAP within 48 h of ang II | 10 used ang III as first agent, and 4 as second-line agent | COVID-19 infection-associated vasodilatory shock | PaO2/FiO2: * 121.4 (98.1–218.1) vs. 200.0 (168.0–248.5) MAP change: * 71 (65–79) vs. 85 (80–87) |
Chawla et al., 2014 [16] | RCT (1 center), USA Follow-up: 30 days |
| Ang II (n = 10) Placebo (n = 10) | Ang II: 68 ± 17 Placebo: 57 ± 12 | Ang II: 60% Placebo: 90% | NE dose to maintain MAP of 65 mmHg | Ang II: NE: 19.80 ± 11.67 mcg/min Vasopressin: 0.02 ± 0.03 unit/min Placebo: NE: 30.30 ± 20.37 mcg/min Vasopressin: 0.05 ± 0.02 unit/min | High output shock | In-hospital mortality: 50% vs. 60%; p-value 1 MAP change at 3 h: 73.1 ± 12.5 vs. 68.8 ± 7.0 Multiorgan failure: 20% vs. 30%; p-value 1 AF: 20% vs. 0; p-value 0.47 |
Wieruszewski et al., 2023 [18] | Retrospective study (4 centers), USA Follow-up: 28 days |
| Ang II (n = 50) Divided: Cardiac failure (n = 41) Respiratory failure (n = 9) | Cardiac failure: * 62 (47–71) Respiratory failure: * 49 (38–64) | Cardiac failure: 88% Respiratory failure: 78% |
| NE-equivalent dose: * Cardiac failure: 0.44 (0.34–0.64) Respiratory failure: 0.47 (0.33–0.73) | Sepsis shock: Cardiac failure: 17% Respiratory failure: 78% Cardiogenic shock: Cardiac failure: 34% Respiratory failure: 0 Vasoplegic shock: Cardiac failure: 73% Respiratory failure: 11% Hemorrhagic shock: Cardiac failure: 17% Respiratory failure: 0 Obstructive shock: Cardiac failure: 7% Respiratory failure: 0 Others: Cardiac failure: 5% Respiratory failure: 11% | MAP change: * Cardiac failure: 60 (57–73) vs. 70 (67–85); p-value < 0.001 Respiratory failure: 61 (57–72) vs. 81 (70–84); p-value 0.26 NE-equivalent dose change: Cardiac failure: Declined by 0.16 mcg/kg/min; p-value < 0.001 Respiratory failure: Decline by 0.13 mcg/kg/min; p-value 0.06 Mortality at 28 days: Cardiac failure: 54% Respiratory failure: 22% |
See et al., 2023 [19] | Prospective observational study (1 center), Australia Follow-up: 90 days |
| Ang II as primary vasopressor (n = 40) vs. Control: conventional vasopressors (n = 80) | Ang II: 62 ± 12 Control: 63 ± 14 | Ang II: 70% Control: 64% |
| Ang II: * NE: 12 (7–18) mcg/min Vasopressin: 0.04 (0.02–0.04) unit/min Epinephrine: 5 (5–5) mcg/min Control: * NE: 10 (5–20) mcg/min Vasopressin: 0.04 (0.04–0.04) unit/min Epinephrine 5 (4–9) mcg/min | Sepsis: Ang II: 60% Control: 55% Pancreatitis: Ang II: 5% Control: 0 Post-operative: Ang II: 15% Control: 16% Multifactorial: Ang II: 10% Control: 11% Others: Ang II: 10% Control: 18% | Peak creatinine at day 7: * 128 (89–192) vs. 126 (91–174); p-value = 0.81 Mortality at 28 days: 18% vs. 29%; p-value = 0.18 Mortality at 90 days: 22% vs. 30%; p-value = 0.39 |
3.2. Risk of Bias Assessment
3.3. Clinical Outcomes
3.3.1. In-Hospital Mortality
3.3.2. MAP Change
3.3.3. Safety Outcomes
3.4. Certainty of Evidence Assessment
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Outcome | Studies | Risk of Bias | Inconsistency | Indirectness | Imprecision | Publication Bias | Overall |
---|---|---|---|---|---|---|---|
Mortality | 2 RCTs, 1 observational | Not serious | Not serious | Not serious | Serious * (−1) | Not serious ** | ⊕⊕⊕⊘ |
MAP Change | 2 RCTs | Not serious | Not serious | Not serious | Not serious | Not serious ** | ⊕⊕⊕⊕ |
Multi-Organ Failure | 2 RCTs | Not serious | Not serious | Not serious | Serious * (−1) | Not serious ** | ⊕⊕⊕⊘ |
Atrial Fibrillation | 2 RCTs | Not serious | Not serious | Not serious | Serious * (−1) | Not serious ** | ⊕⊕⊕⊘ |
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Alamami, A.; Rahhal, A.; Alqudah, B.; Shebani, A.; Alammora, A.; Mohammad, H.; Omar, A.S.; Shehatta, A.L. Clinical Outcomes of Angiotensin II Therapy in Vasoplegic Shock: A Systematic Review and Meta-Analysis. Life 2024, 14, 1085. https://doi.org/10.3390/life14091085
Alamami A, Rahhal A, Alqudah B, Shebani A, Alammora A, Mohammad H, Omar AS, Shehatta AL. Clinical Outcomes of Angiotensin II Therapy in Vasoplegic Shock: A Systematic Review and Meta-Analysis. Life. 2024; 14(9):1085. https://doi.org/10.3390/life14091085
Chicago/Turabian StyleAlamami, Ans, Alaa Rahhal, Bara Alqudah, Ahmed Shebani, Abdelkarim Alammora, Hashim Mohammad, Amr S. Omar, and Ahmed Labib Shehatta. 2024. "Clinical Outcomes of Angiotensin II Therapy in Vasoplegic Shock: A Systematic Review and Meta-Analysis" Life 14, no. 9: 1085. https://doi.org/10.3390/life14091085