Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation

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Analysis 1.1

Comparison 1 Neurological Outcome: cooling vs. no cooling, Outcome 1 Good neurological outcome.

Analysis 2.1

Comparison 2 Survival: cooling vs. no cooling, Outcome 1 Survival.

Table 1. Subgroup Analyses

Outcome_or_Subgroup____________________________________	Studies	Participants	Risk_Ratio__________ (M‐H, Fixed, 95% CI)
Good neurological outcome by cardiac cause vs non‐cardiac cause	3	383	1.54 [1.22, 1.95]
Cardiac cause	3	372	1.51 [1.19, 1.91]
Non‐cardiac cause	2	11	3.80 [0.55, 26.29]
Good neurological outcome by location of cardiac arrest	3	382	1.56 [1.23, 1.98]
In‐hospital	1	17	1.64 [0.47, 5.73]
Out‐of‐hospital	3	365	1.56 [1.23, 1.99]
Good neurological outcome by witnessed cardiac arrest	3	382	1.49 [1.18, 1.88]
Witnessed cardiac arrest	3	360	1.43 [1.13, 1.81]
Non‐witnessed cardiac arrest	3	22	5.31 [1.40, 20.21]
Good neurological outcome by primary ECG rhythm	3	382	1.51 [1.19, 1.91]
VF/VT rhythm	2	330	1.47 [1.15, 1.88]
Non‐ VF/VT rhythm	2	52	2.17 [0.68, 6.93]

Table 1. Subgroup Analyses

Table 2. Adverse Events

Outcome_or_Subgroup___________	Studies	Participants	Risk_Ratio__________ (M‐H, Fixed, 95%CI)
Bleeding of any severity	1	273	1.38 [0.88, 2.16]
Need for platelet transfusion	1	273	5.11 [0.25, 105.47]
Pneumonia	1	273	1.27 [0.90, 1.78]
Sepsis	1	273	1.93 [0.89, 1.78]
Pancreatitis	1	273	0.51 [0.05, 5.57]
Renal failure or oliguria	2	303	0.88 [0.48, 1.61]
Haemodialysis	2	350	1.11 [0.41, 3.01]
Pulmonary edema	1	273	1.76 [0.61, 5.12]
Seizures	1	273	0.89 [0.39, 2.02]
Lethal or long lasting arrhythmia	2	315	1.21 [0.88, 1.67]
Pressure sores	1	273	Not estimable
Significant haemorrhagic complications	1	77	Not estimable
Cardiac complications	1	77	0.16 [0.01, 3.21]
Hypokalaemia	1	42	0.91 [0.31, 2.68]
Hypophosphataemia	1	42	1.12 [0.65, 2.25]

Table 2. Adverse Events

Table 3. Sensitivity Analysis

Outcome_or_Subgroup_____________________________________	Studies	Participants	Risk_Ratio__________ (M‐H, Fixed, 95%CI)
Good neurological outcome all studies	5	479	1.55 [1.24, 1.94]
Studies with conventional cooling and adequate allocation concealment	2	306	1.50 [1.16, 1.93]
Studies with conventional cooling and inadequate or unknown allocation concealment	1	77	1.84 [0.97, 3.49]
Studies with other cooling methods and adequate allocation concealment	1	42	0.71 [0.32, 1.54]
Studies with other cooling method and inadequate or unknown allocation concealment	1	54	4.50 [1.17, 17.30]

Table 3. Sensitivity Analysis

Comparison 1. Neurological Outcome: cooling vs. no cooling

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Good neurological outcome Show forest plot	5	479	Risk Ratio (M‐H, Fixed, 95% CI)	1.55 [1.24, 1.94]

1.1 Conventional cooling without extracorporal methods (IPD, best ever reached CPC of 1 or 2 during hospital stay)	3	383	Risk Ratio (M‐H, Fixed, 95% CI)	1.55 [1.22, 1.96]
1.2 Cooling with haemofiltration (no IPD, CPC of 1 or 2 at six months)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.32, 1.54]
1.3 Unknown method (no IPD, Glasgow Outcome scale of 1‐3 at one month)	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	4.5 [1.17, 17.30]

Comparison 1. Neurological Outcome: cooling vs. no cooling

Comparison 2. Survival: cooling vs. no cooling

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Survival Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Conventional cooling without extracorporal methods (IPD, survival to discharge)	3	383	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [1.10, 1.65]
1.2 Cooling with haemofiltration (no IPD, six‐months survival))	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.32, 1.54]

Comparison 2. Survival: cooling vs. no cooling