Table 1.
Clinical trials of therapeutic hypothermia in adults with ischemic stroke
| Study | n patients: TH/controls | Induction time from symptoms (h) | Duration (h) | Target temperature (°C) | Time to target temperature (°C) | TH method | Complications | Clinical outcomes |
|---|---|---|---|---|---|---|---|---|
| Abou-Chebl et al., 2004[25] | 18/0 | Not specified | Not Specified | 32.0 | 3.2 | Systemic surface | Hypotension, bradycardia, hypokalemia, pneumonia, fever, arrhythmia, MI, transtentorial herniation, ICH, coagulopathy, pancreatitis | Not specified |
| Berger et al., 2002[24] | 12/0 | 16.3 | Not specified | 33.0 | Not specified | Systemic surface | Not specified | Not specified |
| Bi et al., 2011[26] | 31/62 | 6.0 | 24.0 | Not specified | 0.28 | Selective surface; head and neck | Symptomatic ICH, hemorrhage, pneumonia | BI, mRS, NIHSS |
| Chen et al., 2016[27] | 26/0 | 8.0 | 0.17 | Not specified | Not specified | Selective endovascular | Pneumonia, neurological deterioration, vascular spasm, coagulopathy, DVT, melena | Not specified |
| De Georgia et al., 2004[28] | 18/22 | 8.6 | 24.0 | 33.0 | 1.3 | Systemic endovascular | Symptomatic hemorrhagic transformation, DVT, pneumonia, pulmonary edema, cardiogenic shock, tachycardia | mRS, NIHSS |
| Els et al., 2006[29] | 12/13 | Not specified | 48.0 | 35.0 | 2.0 | Systemic combined | Bradycardia | mRS, NIHSS |
| Georgiadis et al., 2001[30] | 6/0 | 28.2 | 67.0 | 34.5 | 3.0 | Systemic endovascular | Pneumonia, hypotension, bradycardia, arrhythmia, thrombocytopenia, hypokalemia | Not specified |
| Georgiadis et al., 2002[31] | 19/17 | 24.0 | 71.0 | 33.0 | 4.0 | Systemic combined | Pneumonia, arrhythmia, bradycardia, thrombocytopenia, hypokalemia | Not specified |
| Geurts et al., 2017[32] | 16/6 | 4.5 | 24.0 | 34.0, 34.5, 35.0 | Not specified | Systemic combined | Pneumonia, UTI, neurological deterioration, ICH, hypertension, bradycardia, tachycardia, hypokalemia, hyponatremia | mRS, NIHSS |
| Hemmen et al., 2010[13] | 28/30 | 6.0 | 24.0 | 33.0 | 2.3 | Systemic endovascular | ICH, pneumonia, DVT | mRS, NIHSS |
| Hoedemaekers et al., 2007[33] | 50/0 | Not specified | Not specified | Varied by method | Not specified | Five systemic methods | Hypotension, arrhythmia | Not specified |
| Hong et al., 2014[34] | 39/36 | 3.0 | 48.0 | 34.5 | 6.3 | Systemic combined | Bradycardia, hypotension, hypokalemia, pulmonary edema, pneumonia | mRS |
| Horn et al., 2013[35] | 20/0 | 5.4 | 12.1 | 33.0 | 1.1 | Systemic combined | Hemorrhagic transformation, pneumonia, bradycardia, hypotension | mRS, NIHSS |
| Kammersgaard et al., 2000[36] | 17/56 | 3.3 | 6.0 | Not specified | Not specified | Systemic surface | Not specified | SSS |
| Kollmar et al., 2009[37] | 10/0 | 2.1 | 4.0 | Not specified | 0.87 | Systemic endovascular | Not specified | NIHSS |
| Krieger et al., 2001[38] | 10/9 | 6.2 | 47.4 | 32.0 | 3.5 | Systemic surface | Pneumonia, fever, sepsis, bradycardia, hypotension, MI, CHF, melena, groin hematoma, ICH, herniation | mRS |
| Lyden et al., 2016[39] | 63/57 | 3.0 | 24.0 | 33.0 | ≤6 | Systemic combined | Pneumonia | BI, mRS, NIHSS |
| Martin-Schild et al., 2009[40] | 20/0 | 5.0 | 24.0 | 33.0–35.0 | ≤2.5 | Systemic combined | Neurological deterioration, bradycardia, cardiac arrest, new brainstem stroke | mRS, NIHSS |
| Milhaud et al., 2004[41] | 12/0 | 10.1 | 448.8 | 32.0–33.0 | 14.5 | Systemic surface | Hypotension, thrombocytopenia, hyperfibrinogenemia, pnuemonia | BI, NIHSS, mRS |
| Neugebauer et al., 2019[42] | 26/24 | Not specified | 72.0 | 33.0 | Not specified | Systemic combined | Pneumonia, cardiovascular events, neurological events | BI, GCS, mRS, NIHSS |
| Ovesen et al., 2013[43] | 17/14 | Not specified | 24.0 | 33.0 | 14.9 | Systemic combined | Pneumonia, asymptomatic hemorrhagic transformation, bradycardia, arrhythmia, pneumothorax, respiratory failure, MI | mRS |
| Peng et al., 2016[44] | 11/15 | Not specified | Not specified | Not specified | Not specified | Selective endovascular | Not specified | NIHSS |
| Piironen et al., 2014[45] | 18/18 | 6.0 | 12.0 | 35.0 | 4.5 | Systemic combined | Pneumonia, CHF, arrhythmia, acute MI, symptomatic ICH, symptomatic brain edema | BI, mRS, NIHSS |
| Poli et al., 2014 | 10/10 | Not specified | 0.5-1.0 | Not specified | Not specified | Systemic or surface endovascular | Not specified | mRS |
| Schwab et al., 1998[46] | 25/0 | 14.0 | Not Specified | 33.0 | Not specified | Systemic combined | Pneumonia, septic syndrome, asymptomatic thrombocytopenia, hypokalemia, cardiac arrhythmias, bradycardia | BI, SSS |
| Schwab et al., 2001[47] | 50/0 | 22.0 | 55.0 | 32.0–33.0 | 6.5 | Systemic surface | Thrombocytopenia, bradycardia, pneumonia | mRS, NIHSS |
| Steiner et al., 2001[48] | 15/0 | Not specified | 72.0 | 32.0–33.0 | Not specified | Systemic surface | Pulmonary infections, septic syndrome, arrhythmia, coagulopathy, pancreatitis | Not specified |
| Su et al., 2016[49] | 16/17 | 42.0 | Not specified | 33.0–34.0 | Not specified | Systemic endovascular | Hemorrhagic transformation, bradycardia, tachycardia, arrhythmia, hypotension, pneumonia, DVT, acute kidney injury, acute liver injury, coagulopathy, GIB | mRS |
| Wu et al., 2018[50] | 45/68 | 5.7 | 0.17 | Not specified | Not specified | Selective endovascular | ICH, pneumonia, UTI, coagulopathy | mRS |
Induction of TH from symptom onset, duration of TH, target temperature, and time to target temperature are described as the reported averages. BI: Barthel index, CHF: Congestive heart failure, DVT: Deep vein thrombosis, GCS: Glasgow Coma Scale, GIB: Gastrointestinal bleed, ICH: Intracerebral hemorrhage, mRS: Modified Rankin Scale, MI: Myocardial infarction, NIHSS: National Institutes of Health Stroke Scale, SSS: Scandinavian Stroke Scale, TH: Therapeutic hypothermia, UTI: Urinary tract infection