Introduction
Materials and methods
Search strategy
Study selection
Data abstraction and study quality
LOE 1
| Randomized controlled trials (RCTs) or meta-analyses of RCTs |
LOE 2
| Studies using concurrent controls without true randomization or meta-analyses of such studies |
LOE 3
| Studies using retrospective controls |
LOE 4
| Studies without a control group (for example, cases series) |
LOE 5
| Studies not directly related to the specific population (for example, different patients, animal models, mechanical models, and so on) |
Review end-points
Results
Search results
Quality of Evidence
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Good
| ** Castrén, ABCD | ||||
* Castrén, E | ||||||
Fair
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Poor
| * Garrett, A | |||||
** Garrett, BCD | * Bruel, E | |||||
** Callaway, E | * Kämärainen, E | |||||
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Level of Evidence
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STATUS | NCT | STUDY |
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Active, recruiting | NCT01400373 | PRINCESS: Prehospital Resuscitation Intra Nasal Cooling Effectiveness Survival Study |
Active, recruiting | NCT00886184 | HITUPPAC-BIO: Intra-arrest therapeutic hypothermia in pre-hospital cardiac arrest |
Active, recruiting | NCT01413399 | A pilot study of intra-arrest hypothermia in patients suffering non-traumatic out-of-hospital cardiac arrest |
Active, recruiting | NCT01173393 | Rapid Infusion of Cold Normal Saline During CPR for Patients With Non-VF Out-of-hospital Cardiac Arrest (RINSE) |
SYSTEMIC COOLING | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Outcomes | IATH (%) | NT (%) | PATH (%) | Species | N | Arrest | Rhythm | No-flow (min) | HT method | IATH core temp (°C) | Time to ROSC (min) | |
Abella [8] | Survival (%, 3 days) | 60 | 10* | 10* | Mice | 30 | KCl | NA | 8 | Ice-water blanket | 30 | 10 to 11 |
GNO (%, 3 days) | 60 | 10* | 10* | |||||||||
ROSC (%) | 100 | 100 | 100 | |||||||||
Albaghdadi [35] | ROSC (%) | 78 | 45 | Pigs | 20 | Asphyxia | NA | 5 | PFC-TLV | 36 | 11 to 13 | |
CoPP (mmHg) | 14 | 14 | ||||||||||
Boddicker [28] | Survival (%, 24 hrs) | 87 | 0* | Pigs | 32 | EC | VF | 8 | Surrounding the body with ice | 33 | 12 to 18 | |
GNO (%, 24 hrs) | 87 | 0* | ||||||||||
ROSC (%) | 87 | 0* | ||||||||||
CoPP (mmHg) | 15 | 10 | ||||||||||
Menegazzi [12] | Survival (%, 20 min) | 57 | 36 | Pigs | 28 | EC | VF | 8 | ivfluid | 34 | 13 | |
ROSC (%) | 86 | 43* | ||||||||||
CoPP (mmHg) | 10 | 11 | ||||||||||
Nordmark [22] | Survival (3-hrs) | 80 | 100 | Pigs | 20 | EC | VF | 8 | ivfluid | 36 | 15 to 20 | |
ROSC (%) | 90 | 100 | ||||||||||
Nordmark [25] | Survival (%, 6 hrs) | 100 | 100 | Pigs | 16 | EC | VF | 8 | ivfluid | 33 | 17 | |
LPR > 30 (n) | 29 | 88* | ||||||||||
SjO2 (%, 6 hr) | 100 | 78* | ||||||||||
ROSC (%) | 100 | 100 | ||||||||||
Riter [10] | Survival (%, 1 hr) | 100 | 100 | Pigs | 24 | EC | VF | 11 | PFC-TLV | 35 | 22 | |
ROSC (%) | 88 | 12* | ||||||||||
CoPP (mmHg) | 14 | 10 | ||||||||||
Shaffner [34] | CBF (mL/100 g/min) | 10 | 5* | Dogs | 12 | EC | VF | 6 | Ice | 28 | NA | |
Staffey [15] | ROSC (%) | 82 | 27* | Pigs | 33 | EC | VF | 11 | PFC-TLV | 33 | 22 | |
CoPP (mmHg) | 10 | 10 | ||||||||||
Sterz [6] | Survival (%, 3 days) | 75 | 92 | 84 | Dogs | 36 | EC | VF | 10 | Cold iv fluids | 34 | 16 to 20 |
GNO (%, 3 days) | 50 | 8* | 41 | External cooling | ||||||||
NDS (3 days) | 19 | 36* | 22 | |||||||||
CPP (mmHg) | 55 | 50 | 51 | |||||||||
ROSC (%) | 75 | 92 | 84 | |||||||||
CoPP (mmHg) | 42 | 48 | 43 | |||||||||
Xiao [24] | Survival (%, 3 days) | 100 | 100 | 100 | Rats | 30 | Asphyxia | NA | 5 | Ice water | 34 | 7 |
GNO (%, 3 days) | 100 | 40* | 80 | |||||||||
NDS (3 days) | 1 | 20* | 12* | |||||||||
ROSC (%) | 100 | 100 | 100 | |||||||||
Yannopoulos [13] | ROSC (%) | 100 | 66* | 44 | Pigs | 45 | CVO | VF | 5 | Intravascular catheter | 33 | 20 |
CoPP (mmHg) | 21 | 21 | 20 | |||||||||
LVEF (%) | 32 | 23* | 21* | |||||||||
Zhao [27] | Survival (%, 7 days) | 53 | 0* | Mice | 45 | KCl | NA | 8 | Blankets | 30 | 10 to 11 | |
GNO (%, 3 days) | 66 | 0* | ||||||||||
ROSC (%) | 93 | 80 | ||||||||||
dP/dtmax (mmHg/s) | 6000 | 3800* | ||||||||||
SELECTIVE BRAIN COOLING
| ||||||||||||
Brader [26] | Survival (24 hrs) | 33 | 0 | Dogs | 12 | EC | VF | 4 | Ice bags around the head | 36 | 24 | |
NDS (24 hrs) | 37 | 62* | ||||||||||
ROSC (%) | 82 | 82 | ||||||||||
Cho [32] | Survival (hrs) | 9.3 | 0.1* | Pigs | 16 | EC | VF/PEA | 14 | TNEC | 36 to 37 | 19 to 29 | |
ROSC (%) | 75 | 12* | ||||||||||
CoPP (mmHg) | 25 | 14* | ||||||||||
Gelman [33] | CPP (mmHg) | 26 | 25 | Pigs | 14 | EC | VF | 6 | Cooling cap placed around the head | 38 | NA | |
CBF (mL/100 g/min) | 16 | 18 | ||||||||||
CoPP (mmHg) | 16 | 18 | ||||||||||
MBF (mL/100 g/min) | 43 | 80* | ||||||||||
Guan [29] | Survival (%, 4-days) | 100 | 29* | 86 | Pigs | 24 | EC | VF | 10 | TNEC | 34-35 | 15 to 25 |
NDS (4-days) | 0 | 400* | 0 | |||||||||
Hagioka [23] | Survival (%, 7-days) | 100 | 100 | Rats | 14 | CVO | VF | 5 | NFC | 37 | 6 | |
GNO (%, 7-days) | 100 | 100 | ||||||||||
CPP (mmHg) | 40 | 34 | ||||||||||
HDS | 33 | 71* | ||||||||||
Jeung [21] | Survival (%, 3 days) | 72 | 72 | Dogs | 14 | EC | VF | 9 | CF | 35 | 12 to 15 | |
NDS (3 days) | 18 | 42* | ||||||||||
ROSC (%) | 100 | 100 | ||||||||||
Tsai [30] | Survival (%, 4 days) | 100 | 25* | 63 | Pigs | 24 | EC | VF | 10 | TNEC | 34 | 15 to 25 |
ROSC (%) | 100 | 88 | 88 | |||||||||
CoPP (mmHg) | 21 | 18 | 20 | |||||||||
LVEF (%) | 63 | 52* | 51* | |||||||||
Tsai [31] | Survival (%, 4 days) | 100 | 29* | Pigs | 16 | EC | VF | 10 | TNEC | 34 | 15 to 25 | |
NDS (%, 4 days) | 0 | 400* | ||||||||||
ROSC (%) | 100 | 88 | ||||||||||
CoPP (mmHg) | 21 | 18 | ||||||||||
LVEF (%) | 63 | 53* | ||||||||||
Wang [36] | ROSC (%) | 87 | 25* | Pigs | 16 | EC | VF | 15 | TNEC | 34 | 20 to 30 | |
CoPP (mmHg) | 25 | 16* |
Outcome | IATH (%) | IATH (%) | |
---|---|---|---|
Riter [10] | PFC-TLV | iv fluids | |
Survival (1-hr, %) | 100 | 100 | |
ROSC (%) | 88 | 25 | |
CoPP (mmHg) | 14 | 8 * | |
Yannopoulos [13] | Intravascular catheter | iv fluids | |
ROSC (%) | 100 | 55 * | |
CoPP (mmHg) | 21 | 15 * | |
LVEF (%) | 32 | 17 * | |
Yu [42] | TNEC | iv fluids | |
Survival (%, 4 days) | 57 | 29 | |
ROSC (%) | 100 | 29 * | |
CoPP (mmHg) | 23 | 12 * |
Setting | Method | Pts | CTRL | VF/VT (%) | Δt at admission | Δt vs CTRL | ROSC | Hospital admission | Survival all patients | Survival admitted pts | |
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Callaway [19] | OHCA | Cranial cooling | 22 | Y (NT) | 41 | -0.02°C/min | NS | IATH 33% CTRL 0% | IATH 66% CTRL 15% | IATH 0% CTRL 0% | IATH 0% CTRL 0% |
Bruel [15] | OHCA | Cold iv fluids | 33 | N | 24 | - 2.1°C | NA | 61% | 61% | 12% | 20% |
Kämärainen [20] | OHCA | Cold iv fluids | 17 | N | 59 | -1.34°C | NA | 71% | 64% | 6% | 9% |
Castrén [16] | OHCA | Trans-nasal | 194 | Y (PATH) | 30 | -1.3°C (tymp) | -0.7°C (core) - 1.3°C (tymp) | IATH 38% CTRL 43% | IATH 36% CTRL 42% | IATH 15% CTRL 13% | IATH 44% CTRL 31% |
Garrett [18] | OHCA | Cold iv fluids | 542 | Y (NT) | 22 | NA | NA | IATH 37% CTRL 27% | IATH 28% CTRL 23% | IATH 13% CTRL 12% | IATH 44% CTRL 51% |
Effects on mortality
a) IATH versus normothermia
b) IATH versus PATH
Effects on neurological outcome
a) IATH versus normothermia
b) IATH versus PATH
Effects on brain perfusion and metabolism
a) IATH versus normothermia
b) IATH versus PATH
Effects on cardiac function
a) IATH versus normothermia
b) IATH versus PATH
Effects on coronary perfusion pressure
a) IATH versus normothermia
Effects on return of spontaneous circulation (ROSC)
a) IATH versus normothermia
b) IATH versus PATH
Effects on defibrillation attempts and epinephrine dose
a) IATH versus normothermia
b) IATH versus PATH
Effects of methods of inducing IATH
a) Effects of IATH method on outcomes
b) Effects of time of initiation of IATH
c) Effects of target temperature during IATH
Adverse events
Discussion
Conclusion
Key messages
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IATH improves survival and neurological outcome when compared to normothermia and/or PATH in experimental models of CA.
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IATH prevents the decrease in cardiac function occurring after CA and maintains better cerebral perfusion and metabolism during CPR when compared to normothermia.
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Data on the efficacy of IATH in humans are still limited. One RCT showed better survival and neurological outcome in those patients receiving IATH with a no-flow time less than 10 minutes. Ongoing clinical trials will provide further data on the use of IATH in human CA.
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In the clinical setting, external cranial cooling, cold intravenous fluids and TNEC have been used to induce IATH. Few adverse events have been reported with these techniques.