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. 2018 Jun 21;13(6):e0198676. doi: 10.1371/journal.pone.0198676

Table 1. Systematic review characteristics and quality, with number of included and non-included RCTs.

Systematic review Pop. Intervention (vs comparison) Search RCTs Qual. Non-includ. RCTs
PD* S^ T#
1. Airway, ventilation and oxygenation strategies
Hyperbaric hyperoxia
McDonough 2004[33] All Hyperbaric oxygen therapy** 2003 2 Mod 3 1 1
§Meyer 2010[31] All Hyperbaric oxygen therapy 1980–2008 2 Mod 3 1 1
§Lu 2012[19] Adult Hyperbaric oxygen therapy 2011 2 Low 1 2 2
Bennett 2012[34] All Hyperbaric oxygen therapy 2012 5 High 1 1 0
Hyperventilation
§Roberts 1998[32] All Hyperventilation vs. normovent. 1996 1 Low 0 0 0
Roberts 1997[35] All Hyperventilation 2008 1 Mod 0 0 0
§Meyer 2010[31] All Hyperventilation 1980–2008 1 Mod 0 0 0
§Lu 2012[19] Adult Hyperventilation 2011 1 Low 0 0 0
Management guided by brain tissue oxygen
Nangunoori 2012[36] All PbtO2-based vs ICP/CPP-based** 1993–2010 0 Low 0 5 0
Lazaridis 2014[37] Adult Monitoring (≥ 2: PbtO2, PRx, LPR)** 2013 4 Mod 0 1 0
2. Fluid management
Blood or blood product transfusion
Nishijima 2012[38] Adult Platelet transfusion 2011 0 Mod 0 3 0
†Boutin 2015[39] Adult RBC transfusion 2015 2 High 0 1 0
3. Hypothermia
Hypothermia
Harris 2002[40] Adult Hypothermia vs. normo.** ?2001 7 Mod 14 11 4
McIntyre 2003[41] Adult Hypothermia vs. normo.** 2002 11 High 13 11 1
Henderson 2003[42] All Hypothermia** 2002 8 Mod 21 5 2
Peterson 2008[43] Adult Hypothermia vs. SC 2007 12 Mod 10 6 8
†Saxena 2008[44] All Hypothermia min. 35◦ C 2008 0 High 0 36 0
Sydenham 2009[45] All Hypothermia max. 35◦ C 2009 20 High 10 5 1
§Meyer 2010[31] All Hypothermia 1980–2008 9 Mod 12 5 10
Fox 2010[46] Adult Early hypothermia vs normo.** ?2008 11 High 5 18 2
Sadaka 2012[47] Adult Hypothermia** 2010 8 Low 7 19 2
Georgiou 2013[48] All Systemic hypothermia** 2011 17 High 5 13 1
†Harris 2012[49] Adult Non-invasive head cooling 2011 1 High 0 35 0
§Lu 2012[19] Adult Hypothermia 2011 8 Low 5 5 18
Ma 2013[48] Paed. Hypothermia vs normo.** ?2012 3 Mod 2 31 0
Crossley 2014[50] Adult Hypothermia** 2012 15 High 1 18 2
Li 2014[51] Adult Moderate hypothermia 2012 11 Mod 1 19 5
Madden 2015[52] Adult Hypothermia** 2009–2013 2 Low 1 33 0
Zhang 2015[53] Paed. Hypothermia** 2014 4 Mod 1 31 0
4. Intracranial, Cerebral Perfusion and Blood Pressure management
Hypertonic saline and/or mannitol
§Roberts 1998[32] All Mannitol vs. no mannitol 1996 1 Low 0 17 0
Banks 2008[54] All HTS 2007 4 Low 0 14 0
§Meyer 2010[31] All Mannitol, and/or HTS 1980–2008 10 Low 6 0 2
Wakai 2013[55] All Mannitol 2009 4 High 2 12 0
Kamel 2011[56] All Mannitol vs. HTS** 2010 1 Mod 2 14 1
§Lu 2012[19] Adult Mannitol, and/or HTS 2011 5 Low 3 2 8
Rickard 2014[57] Adult Mannitol vs. HTS** ?2012 3 Mod 0 14 1
Lourens 2014[58] All HTS vs. saline/Lactated Ringers** 2011 3 High 1 13 1
Li 2015[59] Adult Mannitol vs. HTS** 2014 3 Mod 0 15 0
Management guided by intracranial pressure
Mendelson 2012[60] Adult ICP-directed therapy ** 2011 0 Mod 1 1 0
Sadaka 2013[61] Adult Placement of ICP monitors 1993–2011 0 Low 0 2 0
Su 2014[62] All ICP-directed therapy 2013 1 Mod 0 1 0
Yuan 2015[63] Adult ICP Monitoring** 2013 1 Mod 0 1 0
†Forsyth 2015[64] All ICP-directed therapy 2015 1 High 0 1 0
Cerebrospinal fluid drainage
§Roberts 1998[32] All CSF drainage vs no drainage 1996 0 Low 1 0 0
§Meyer 2010[31] All CSF drainage 1980–2008 1 Mod 0 0 0
Posture
Fan 2004[65] All Therapeutic body positioning** 2003 1 Low 0 0 1
§Meyer 2010[31] All Adjusting head posture 1980–2008 2 Mod 0 0 0
§Meyer 2010[31] All Body rotation 1980–2008 0 Mod 0 2 0
Pressure: other
†Muzevic 2013[66] All The Lund concept 2013 0 High 0 0 0
5. Nutrition and glucose management
Nutrition: timing, delivery route and nutritional elements
Krakau 2006[67] Adult Feeding timing, routes, content** 1993–2003 8 Mod 8 5 1
Perel 2006 [68] All Feeding timing & routes 2006 7 High 2 13 0
§Lu 2012[19] Adult Early nutritional support 2011 3 Low 2 5 12
Wang 2013[69] All Feeding timing, routes, elements** 2012 10 High 0 8 4
Wang 2015[70] All Sm. intestine vs gastric feeding** 2013 3 Mod 0 18 1
Nutrition: Insulin
Lei 2012[71] Adult Tight vs. conv. glycaemic control 2011 4 Mod 1 0 0
§Lu 2012[19] Adult Insulin therapy 2011 3 Low 1 1 0
6. Pharmacological therapies not elsewhere defined
Progesterone
§Meyer 2010[31] All Progesterone 1980–2008 2 Low 5 0 0
§Lu 2012[19] Adult Progesterone 2011 2 Low 5 0 0
Ma 2012[47] All Progesterone vs. placebo 2012 2 High 5 0 0
Wang 2015[72] All Progesterone** 1980–2015 5 High 0 0 2
†Zeng 2015[73] All Progesterone 2015 6 High 0 1 0
Bradykinin antagonists
§Meyer 2010[31] All Bradykinin antagonists 1980–2008 3 Low 1 0 0
§Lu 2012[19] Adult Bradykinin antagonists 2011 1 Low 0 1 2
Calcium channel blockers
Langham 2003[74] All Calcium channel blockers 2005 4 Mod 0 0 0
§Lu 2012[19] Adult Calcium channel blockers 2011 3 Low 0 0 1
Antifibrinolytic agents
Perel 2010[75] All Haemostatic agents 2009 2 High 2 0 0
§Lu 2012[19] Adult Haemostatic agents 2011 1 Low 1 0 2
†Zehtabchi 2014[76] All Tranexamic acid 2014 2 High 0 2 0
†Ker 2015[77] All Antifibrinolytic agents 2015 2 High 0 2 0
Monoaminergic agonists
Siddall 2005[78] All Methylphenidate 2004 0 Low 0 0 0
§Meyer 2010[31] All Dopamine targeting agents** 1980–2008 0 Mod 0 0 0
†Forsyth 2006[79] All Monoaminergic agonists 2009 0 High 0 0 0
Frenette 2012[80] All Dopamine agonists 2010 0 Mod 0 0 0
§Lu 2012[19] Adult Monoaminergic agonists 2011 0 Low 0 0 0
Aminosteroids
†Roberts 1999[81] All Aminosteroid vs. Placebo 2006 1 High 0 0 0
§Lu 2012[19] Adult Tirilazad 2011 1 Low 0 0 0
Pharmacological therapies not elsewhere defined: various (single topic)
§Meyer 2010[31] All Dimethyl sulphoxide 1980–2008 0 Low 0 0 0
§Lu 2012[19] Adult Pegogortein 2011 1 Low 0 0 0
†Alali 2014[82] Adult Beta-blockers 2013 1 High 0 0 0
Shen 2015[83] All Anticoagulants** 2013 2 Mod 0 0 0
†Zeiler 2014[84] All Tromethamine** 2014 3 High 0 0 0
Sanfilippo 2015[85] Adult Neuromuscular blocking agents 2014 3 Low 0 0 0
7. Glutamate receptor antagonists
Magnesium
Arango 2008[86] All Magnesium vs. control 2008 1 High 2 0 0
Li 2015[87] All Magnesium** 2013 3 Mod 0 0 0
Glutamate receptor agonists: general
Willis 2003[88] All EAAI vs. control** 2002 2 High 5 0 0
§Meyer 2010[31] All Cannabinoids 1980–2008 2 Low 0 5 0
§Lu 2012[19] Adult EAAI 2011 4 Low 1 0 2
8. Prehospital and systems of care
Prehospital intubation
§Lu 2012[19] Adult Pre-hospital RSI 2011 1 Low 0 0 0
†Bossers 2015[89] Adult Prehospital intubation** 2015 1 High 0 0 0
Specialist versus general hospital transfer or care
Pickering 2015[90] All Prehospital transfer strategies 1998–2012 0 Mod 1 0 0
†Fuller 2014[91] Adult Specialist neuroscience care 2013 0 High 0 1 0
9. Sedation, Pain management, Anaesthesia and Arousal
Sedative agents
§Meyer 2010[31] All Opiods, propofol, midazolam 1980–2008 3 Mod 2 1 6
Roberts 2011[92] All Range of sedative agents 2010 10 High 2 0 0
Gu 2014[93] All Midazolam vs. propofol 2013 2 Mod 0 10 0
Ketamine
Zeiler 2014[94] All Ketamine** 2013 2 High 1 0 0
Wang 2014[95] All Ketamine vs opiods** 2014 2 Mod 0 0 1
Cohen 2015[87] Adult Ketamine** 2014 3 Mod 0 0 0
Barbiturates
§Roberts 1998[32] All Barbiturates vs. no barbiturates 1996 2 Low 0 5 2
§Meyer 2010[31] All Barbiturates 1980–2008 3 Low 2 1 3
§Lu 2012[19] Adult Barbiturates 2011 2 Low 1 1 5
Roberts 2012[96] All Barbiturates 2012 6 High 0 1 2
Stimulation
§Meyer 2010[31] All Stimulation; sensory, electrical 1980–2008 3 Mod. 1 0 0
†Wong 2013[97] All Acupuncture 2012 0 High 0 0 0
Burst suppression
Zeiler 2015[98] All Burst suppression** 2015 1 High 0 18 2
10. Seizure prophylaxis
Anti-epileptic agents
Schierhout 1998[99] All Anti-epileptic agents 1996 4 Mod 5 3 1
Teasell 2007[100] All Any seizure interventions 1980–2005 4 Mod 3 4 2
Zafar 2012[101] All Phenytoin vs. levetiracetam 2011 0 High 0 12 1
Thompson 2015[102] All Anti-epileptic, neuroprot. agents** 2015 8 High 1 4 0
11. Steroids
Corticosteroids
§Roberts 1998[32] All Corticosteroids vs. no corticost. 1996 11 Low 2 3 3
Alderson 2005[103] All Corticosteroids vs. control 2008 16 High 1 2 0
§Meyer 2010[31] All Corticosteroids 1980–2008 7 Low 1 5 6
§Lu 2012[19] Adult Corticosteroids 2011 6 Low 1 0 12
12. Surgery
Surgery: compared with no surgery and/or with different surgical techniques
Sahuquillo 2006[104] All Decompressive craniectomy 2008 1 High 4 5 0
§Meyer 2010[31] All Decompressive craniectomy 1980–2008 2 Mod 7 0 1
Jacob 2011[105] Paed. Decompressive craniectomy** 1997–2008 0 Low 0 9 1
Guresir 2012[106] Paed. Decompressive craniectomy 2010 0 Low 0 9 1
Bor-Seng-Shu 2012[107] All Decompressive craniectomy** 2010 1 Low 1 8 0
§Lu 2012[19] Adult Decompressive craniectomy 2011 3 Low 6 0 1
Wang 2015[108] All Decompressive craniectomy** 2015 3 Mod 2 4 1
Surgery: timing of surgery (n = 10 RCTs in total)
Kim 2014[109] All Time to surgery** 1990–2013 2 Low 0 8 0

*Post-dates the systematic review: RCT published subsequent to the systematic review, but would otherwise have met the review inclusion criteria (score of 0 means the review is ‘current’)

^Out of scope: RCT did not meet the systematic review inclusion criteria irrespective of when it was published. RCTs that post-dated a review but would not have met the inclusion criteria were coded to this category.

#True Missing: RCT was published within review search dates and looks to have met the review inclusion criteria (score of 0 means the review is ‘complete’)

†Systematic review was judged to be current, complete and high quality

§Multi-intervention review (included more than one intervention type)

**Included one or more outcomes as inclusion criteria

Abbreviations: Conv. = conventional; Corticost. = corticosteroids; CPP = central perfusion pressure; CSF = cerebrospinal fluid; EAAI = excitatory amino acid inhibitors; Endotrach = endotracheal, HTS = hypertonic saline; ICP = intracranial pressure; Includ. = included, Mod. = moderate; Neuroprot = neuroprotective agents; Normo. = normothermia; Normovent. = normoventilation; Paed. = paediatric; PbtO2 = brain tissue oxygen; Pop. = population; PD = post-date the review; Qual. = quality; RBC = red blood cells, RCTs = randomised controlled trials; RSI = rapid sequence intubation; Rx = treatment; S = out of scope; Sm = small, T = true missing, Vs. = versus