Is there an optimal ICP treatment threshold the maintenance of which is critical to optimize recovery?

Reference	# of patients	Design	Grade crit.	Results	Caveats
Miller et al., 1977 [58]	160	Single-centre retrospective case series	Low	No ICP threshold for outcome in patients with mass lesion. When ICP was 0–10 mmHg in patients without mass lesions, 85 % made a good recovery (GOS 4–5) and 8 % died. When ICP was 11– 20 mmHg, good recovery rate was 64 and 25 % died (χ2 = 5.30; p < 0.02)	All patients treated for elevated ICP. Minimal risk adjustment or multifactorial analysis
Nordby and Gunnerod, 1985 [47]	130	Single-centre retrospective case series	Low	Significantly worse outcome in patients whose ICP exceeded 20 mmHg (p < 0.001). ICP ≥ 40 mmHg had high risk of progressing to brain death	All patients treated for elevated ICP. Minimal risk adjustment or multifactorial analysis. Epidural monitoring
Marshall et al. 1979 [72]	100	Single-centre retrospective case series	Low	For patients without mass lesions with ICP < 15 mmHg, 77 % achieved favorable outcome (GOS = 4–5) versus those with ICP ≥ 15 mmHg for ≥15 min, wherein 42 % achieved favourable outcome (p < 0.01 by univariate analysis). Favorable outcomes were achieved in 43 % with ICP ≥ 15 for 15 min and in 42 % with ICP > 40 mmHg for 15 min	All patients treated for ICP > 15 mmHg. Minimal risk adjustment or multifactorial analysis
Saul and Ducker, 1982 [37]	233	Single-centre, retrospective, sequential case series’ comparing two protocols	Low	Mortality rate was 46 % for those treated with a 20–25 mmHg threshold protocol versus 28 % for those treated with a 15 mmHg protocol (p < 0.0005 by univariate analysis). For those with ICP’s ≥ 25 mmHg, respective mortality was 84 versus 69 % (p < 0.05). For those with ICP’s ≤ 25 mmHg, respective mortalities were 26 % and 15 % (p < 0.025)	Threshold analysis confounded by concomitant general protocol effects. Minimal risk adjustment or multifactorial analysis
Marmarou et al. 2005 [85]	428	Multi-centre retrospective analysis of prospectively collected database	Low	The proportion of measurements with ICP > 20 mmHg was the most powerful predictor of 6 month outcome after age, admission GCS motor score, and abnormal admission pupils. The full model correctly explained 53 % of observed outcomes. ICP proportion modeling power peaked at 20 mmHg	Confounding by choice of threshold, variable responses to supra-threshold values of different magnitudes, the beneficial and toxic effects of treatments, and the interaction of ICP with other variables in individual patients. Their model assumes equal effect of each descriptor over its entire range
Chambers et al. 2001 [87]	207 adults	Single-centre retrospective observational study	Low	ROC analysis of maximum ICP from hourly averages of automated ICP data found optimal prediction of 6 month dichotomized GOS outcome to be 35 mmHg	Studied only maximal ICP values
Ratanalert et al. 2004 [86]	27	Prospective randomized trial of protocolised treatment at two different ICP thresholds (20 vs. 25 mmHg)	Low	No significant difference in 6-month GOS by univariate or multivariate analysis	Very small sample size. Little detail provided on study design and management
Smith et al. 1986 [80]	77	Prospective randomized trial of patients treated based on ICP versus scheduled treatment	Low	No significant difference in 1 year GOS by univariate analysis. Mean ICP 5.5 mmHg higher in monitorbased-treatment group	Small sample size. Investigation not designed to study ICP threshold
Resnick et al. 1997 [88]	37	Single-centre retrospective observational study on patients with ICP > 20 mmHg that persisted for >96 h	Low	38 % reached GOS 4–5 at ≥6 months; 43 % GOS 1–2. Patients < 30 years had better outcome, 57 % reaching GOS 4–5 versus 12.5 % (p < 0.02). Patients with good outcomes were significantly younger (p = 0.0098). The association of age and GCS with outcome was significant (p < 0.005)	No detail on the degree of ICP resistance or magnitude of related insults (low CPP, herniation)
Young et al. 2003 [89]	9	Single-centre retrospective observational study of patients with ICP > 25 for ≥2 h	Low	Mortality = 56 %. 44 % survived, with GOS = 4 at rehabilitation discharge	Small series. No quantification of ICP or CPP insults. No comparison to those who died
Vik et al. 2008 [53]	93	Single-centre retrospective observational trial analyzing ICP as AUC	Low	The dose of ICP was an independent predictor of death (OR 1.04; 95 % CI 1.003–1.08; p = 0.035) and poor outcome (OR 1.05; 95 % CI 1.003–1.09; p = 0.034) at 6 months, by multiple regression	No control for monitoring duration or terminal events. Arbitrary stratification of AUC categories
Kahraman et al. 2010 [90]	30	Single-centre retrospective observational trial using prospective data analyzing manual versus automated ICP as AUC versus mean	Low	For automated data, total ICU AUC had high predictive power for GOS-E 1–4 (area under the ROC curve = 0.92 ± 0.05) and moderate predictive power for in-hospital mortality (0.76 ± 0.15). The percentage of monitoring time that ICP > 20 mmHg had significantly lower predictive power for 3 month GOS-E compared with AUC using 20 mmHg as the cutoff (p = 0.016)