Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea
Abstract
:1. Introduction
2. Results
2.1. Baseline Demographics
2.2. Types of ADEs Induced by Sedatives
2.3. Factors Associated with Seriousness of Sedative-Related ADEs
3. Discussion
4. Materials and Methods
4.1. Data Source and Definitions
4.2. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Serious AEs (n = 3132) | Nonserious AEs (n = 92,056) | Total AE Cases (n = 95,188) | |
---|---|---|---|
Alfentanil | 3 (0.1) | 671 (0.7) | 674 (0.7) |
Dexmedetomidine | 65 (2.1) | 252 (0.3) | 317 (0.3) |
Diazepam | 127 (4.1) | 2214 (2.4) | 2341 (2.5) |
Etomidate | 48 (1.5) | 126 (0.1) | 174 (0.2) |
Fentanyl | 809 (25.8) | 55,155 (59.9) | 55,964 (58.8) |
Ketamine | 141 (4.5) | 585 (0.6) | 726 (0.8) |
Midazolam | 484 (15.5) | 4398 (4.8) | 4882 (5.1) |
Pethidine | 996 (31.8) | 23,672 (25.7) | 24,668 (25.9) |
Propofol | 247 (7.9) | 1509 (1.6) | 1756 (1.8) |
Remifentanil | 186 (5.9) | 2691 (2.9) | 2877 (3.0) |
Sufentanil | 2 (0.1) | 405 (0.4) | 407 (0.4) |
Thiopental | 24 (0.8) | 378 (0.4) | 402 (0.4) |
Characteristics | No. of Cases (% Relative Frequency) or Median [Range] |
---|---|
Age a (Years) | 53 [0–115] |
<10 years | 1872 (2.0) |
10–19 years | 4648 (5.1) |
20–29 years | 7300 (8.0) |
30–39 years | 10,588 (11.5) |
40–49 years | 14,908 (16.2) |
50–59 years | 18,743 (20.4) |
60 years or older | 33,707 (36.7) |
Sex b | |
Male | 31,524 (33.4) |
Female | 62,798 (66.6) |
Causality c | |
Certain | 1822 (1.9) |
Probable/likely | 44,214 (46.5) |
Possible | 49,152 (51.6) |
Treatment Duration d (Days) | 0 (0–31) |
<1 day | 45,002 (47.3) |
1 day | 12,756 (13.4) |
2 days | 6780 (7.12) |
3 days | 2727 (2.86) |
≥4 days | 3590 (3.77) |
Seriousness | |
Serious events e | 3132 (3.3) |
Nonserious events | 92,056 (96.7) |
Individuals Reporting the Sedative-Induced AEs f | |
Physicians | 8367 (9.2) |
Pharmacists | 7066 (7.8) |
Nurses | 67,881 (75.0) |
General Public | 78 (0.1) |
Others | 7142 (7.90) |
No. of Medications Used | |
1 | 70,392 (74.0) |
2 | 12,930 (13.6) |
3 | 4994 (5.3) |
4 | 1665 (1.8) |
5 | 814 (0.9) |
6 | 575 (0.6) |
7 | 460 (0.5) |
8 | 364 (0.4) |
≥9 | 2994 (3.1) |
No. of Comorbidities g | |
1 | 61,752 (95.8) |
2 | 1779 (2.8) |
3 | 543 (0.8) |
4 | 160 (0.3) |
≥5 | 237 (0.4) |
SOC Disorder Class | Serious AEs (n = 3132) | Nonserious AEs (n = 92,056) | Total AEs (n = 95,188) | p Value a | ROR (95% CI) b |
---|---|---|---|---|---|
Skin and appendages | 156 (5.0) | 5532 (6.0) | 5688 (6.0) | 0.017 | 0.820 (0.696–0.965) |
Musculoskeletal system | 9 (0.3) | 91 (0.1) | 100 (0.1) | 0.001 | 2.912 (1.467–5.782) |
Collagen | 0 (0.0) | 2 (<0.1) | 2 (<0.1) | N/E c | N/E c |
Central and peripheral nervous system (e.g., decreased consciousness, dizziness) | 470 (15.0) | 23,363 (25.4) | 23,833 (25.0) | <0.001 | 0.519 (0.470–0.573) |
Vision | 10 (0.3) | 82 (0.1) | 92 (0.1) | 0.001 | 3.593 (1.962–6.934) |
Hearing and vestibular | 1 (< 0.1) | 11 (<0.1) | 12 (<0.1) | N/E c | N/E c |
Special senses (other) d | 0 (0.0) | 4 (<0.1) | 4 (<0.1) | N/E c | N/E c |
Psychiatric | 143 (4.6) | 3200 (3.5) | 3343 (3.5) | 0.001 | 1.328 (1.119–1.577) |
Gastrointestinal (e.g., nausea, vomiting) | 260 (8.3) | 51,317 (55.8) | 51,577 (54.2) | <0.001 | 0.720 (0.630–0.820) |
Liver and biliary system | 35 (1.1) | 102 (0.1) | 137 (0.1) | <0.001 | 10.188 (6.928–14.982) |
Metabolic and nutritional | 9 (0.3) | 127 (0.1) | 136 (0.1) | 0.029 | 2.086 (1.060–4.105) |
Endocrine | 0 (0.0) | 2 (<0.1) | 2 (<0.1) | N/Ec | N/E c |
General cardiovascular | 44 (1.4) | 59 (0.1) | 103 (0.1) | <0.001 | 22.218 (15.012–32.882) |
Myocardial, endocardial, pericardial, and valve | 0 (0.0) | 1 (<0.1) | 1 (<0.1) | N/E c | N/E c |
Heart rate and rhythm (e.g., hypotension) | 1038 (33.1) | 2650 (2.9) | 3688 (3.9) | <0.001 | 16.724 (15.379–18.187) |
Vascular (extracardiac) | 11 (0.4) | 72 (0.1) | 83 (0.1) | <0.001 | 4.503 (2.385–8.501) |
Respiratory system (e.g., dyspnea, decreased oxygen saturation) | 608 (19.4) | 995 (1.1) | 1603 (1.7) | <0.001 | 22.046 (19.782–24.569) |
Red blood cell | 3 (0.1) | 9 (<0.1) | 12 (<0.1) | N/E c | N/E c |
White cell and reticuloendothelial system | 16 (0.5) | 50 (0.1) | 66 (0.1) | <0.001 | 9.449 (5.375–16.609) |
Platelet, bleeding, and clotting | 8 (0.3) | 19 (<0.1) | 27 (<0.1) | <0.001 | 12.405 (5.426–28.358) |
Urinary system (e.g., nephrotoxicity) | 51 (1.6) | 1187 (1.3) | 1238 (1.3) | 0.1 | 1.267 (0.955–1.681) |
Reproductive (male) | 2 (0.1) | 0 (0.0) | 2 (<0.1) | N/E c | N/E c |
Reproductive (female) | 9 (0.3) | 9 (<0.1) | 18 (<0.1) | <0.001 | 29.474 (11.692–74.301) |
Fetal | 1 (<0.1) | 1 (<0.1) | 2 (<0.1) | N/E c | N/E c |
Neonatal and infancy | 4 (0.1) | 9 (<0.1) | 13 (<0.1) | <0.001 | 13.079 (4.025–42.492) |
Neoplasms | 0 (0.0) | 1 (<0.1) | 1 (<0.1) | N/E c | N/E c |
Body as a whole—general | 234 (7.5) | 2748 (3.0) | 2982 (3.1) | <0.001 | 2.634 (2.293–3.025) |
Application site | 3 (0.1) | 402 (0.4) | 405 (0.4) | N/E c | N/E c |
Resistance mechanism | 5 (0.2) | 3 (<0.1) | 8 (<0.1) | N/E c | N/E c |
Secondary terms—events e | 2 (0.1) | 6 (<0.1) | 8 (<0.1) | N/E c | N/E c |
Poison specific terms | 0 (0.0) | 2 (<0.1) | 2 (<0.1) | N/E c | N/E c |
Predictors | Univariate Analysis (Number of Cases (%)) | Multivariate Analysis | |||
---|---|---|---|---|---|
Serious AEs (n = 3132) | Nonserious AEs (n = 92,056) | p Value | OR (95% CI) | p Value | |
Sex a | <0.001 | <0.001 | |||
Male | 1460 (46.6) | 30,064 (32.7) | 1.421 (1.318–1.531) | ||
Female | 1622 (51.8) | 61,176 (67.5) | 1 (reference) | ||
Age b | <0.001 | <0.001 | |||
< 10 | 211 (6.7) | 1661 (1.8) | 1 (reference) | ||
10–19 | 130 (4.2) | 4518 (4.9) | 0.499 (0.388–0.642) | ||
20–29 | 164 (5.2) | 7136 (7.8) | 0.413 (0.323–0.528) | ||
30–39 | 249 (8.0) | 10,339 (11.2) | 0.427 (0.340–0.537) | ||
40–49 | 374 (11.9) | 14,534 (15.8) | 0.470 (0.379–0.583) | ||
50–59 | 515 (16.4) | 18,228 (19.8) | 0.486 (0.395–0.599) | ||
≥ 60 | 1388 (44.3) | 32,319 (35.2) | 0.729 (0.599–0.886) | ||
Causality c | <0.001 | <0.001 | |||
Certain | 49 (1.6) | 1773 (1.9) | 1.015 (0.786–1.312) | ||
Probable/likely | 956 (30.5) | 43,258 (47.0) | 0.649 (0.598–0.704) | ||
Possible | 2127 (67.9) | 47,025 (51.1) | 1 (reference) | ||
Etiologic sedative | <0.001 | <0.001 | |||
Alfentanil | 3 (0.5) | 671 (99.5) | 1 (reference) | ||
Dexmedetomidine | 66 (20.8) | 251 (79.2) | 35.784 (11.120–115.153) | ||
Diazepam | 135 (5.8) | 2206 (94.2) | 8.384 (2.652–26.506) | ||
Etomidate | 49 (28.2) | 125 (71.8) | 52.232 (15.943–171.118) | ||
Fentanyl | 819 (1.5) | 55,145 (98.5) | 3.084 (0.989–9.615) | ||
Ketamine | 148 (20.4) | 578 (79.6) | 31.322 (9.865–99.453) | ||
Midazolam | 484 (10.0) | 4398 (90.0) | 18.174 (5.817–56.786) | ||
Pethidine | 1019 (4.1) | 23,649 (95.9) | 7.861 (2.522–24.501) | ||
Propofol | 264 (15.0) | 1492 (85.0) | 27.226 (8.669–85.504) | ||
Remifentanil | 199 (6.9) | 2678 (93.1) | 13.207 (4.200–41.528) | ||
Sufentanil | 2 (0.5) | 405 (99.5) | 0.786 (0.130–4.735) | ||
Thiopental | 30 (7.5) | 372 (92.5) | 11.049 (3.287–37.148) | ||
Number of concurrently used medications | <0.001 | 1.015 (1.000–1.031) | <0.001 | ||
1 | 2062 (65.8) | 68,330 (74.7) | |||
2 | 498 (15.9) | 12,432 (13.6) | |||
3 | 216 (6.9) | 4778 (5.2) | |||
4 | 124 (4.0) | 1541 (1.7) | |||
≥ 5 | 232 (7.4) | 4975 (0.8) | |||
Concomitantly used medication | |||||
Antihistamine | 67 (2.1) | 649 (0.7) | <0.001 | 1.557 (1.096–2.212) | <0.001 |
NSAIDs | 135 (4.3) | 5605 (6.1) | <0.001 | 0.426 (0.343–0.527) | <0.001 |
Opioids | 181 (5.8) | 8137 (8.9) | <0.001 | 0.488 (0.409–0.583) | <0.001 |
5HT3 antagonists | 38 (1.2) | 2574 (2.8) | <0.001 | 0.483 (0.346–0.676) | <0.001 |
ASA | 27 (0.9) | 111 (0.1) | <0.001 | 2.900 (1.771–4.750) | <0.001 |
Neuromuscular blockers | 152 (4.9) | 1383 (1.5) | <0.001 | 1.640 (1.086–1.712) | <0.001 |
Corticosteroids | 98 (3.1) | 609 (0.7) | <0.001 | 2.933 (2.187–3.935) | <0.001 |
Sedatives | 500 (16.0) | 6568 (7.1) | <0.001 | 1.272 (1.121–1.444) | <0.001 |
Benzodiazepines | 51 (1.6) | 324 (0.4) | <0.001 | 2.370 (1.703–3.299) | <0.001 |
Zolpidem | 10 (0.3) | 207 (0.2) | <0.001 | 0.290 (0.142–0.591) | <0.001 |
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Choi, Y.-J.; Yang, S.-W.; Kwack, W.-G.; Lee, J.-K.; Lee, T.-H.; Jang, J.-Y.; Chung, E.-K. Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea. Pharmaceuticals 2021, 14, 783. https://doi.org/10.3390/ph14080783
Choi Y-J, Yang S-W, Kwack W-G, Lee J-K, Lee T-H, Jang J-Y, Chung E-K. Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea. Pharmaceuticals. 2021; 14(8):783. https://doi.org/10.3390/ph14080783
Chicago/Turabian StyleChoi, Yeo-Jin, Seung-Won Yang, Won-Gun Kwack, Jun-Kyu Lee, Tae-Hee Lee, Jae-Yong Jang, and Eun-Kyoung Chung. 2021. "Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea" Pharmaceuticals 14, no. 8: 783. https://doi.org/10.3390/ph14080783