A total of 341 patients met the inclusion criteria for this study (Fig. 1). The study population was predominantly Caucasian (58.1 %) and included a slightly larger proportion of men (56.3 %) with median age of 56.3 years old. On admission to the ICU, the median GCS score was 6 (IQR 3–7). Subarachnoid hemorrhage was the most common diagnosis (37.5 %) followed by intracerebral hemorrhage (23.5 %) and traumatic brain injury (20.5 %). Overall, patients were ventilated for a median of 3.2 days (IQR 1.2–8.9) and experienced a median ICU and hospital length of stay of 11 and 16 days, respectively (Table 1).
Table 2 describes the clinical parameters of the cohort with respect to mechanical ventilation and hemodynamic data closest to each ICP observation, stratified according to the severity of lung injury. Overall, of 28,644 observations (validated paired PEEP and ICP data points), 71.3 % were recorded at times classified as without concurrent lung injury, whereas 15.2 % were recorded at times classified as mild lung injury, 11.6 % as moderate, and 1.9 % as severe.
Observations occurring during periods of severe lung injury experienced higher median PEEP values (10 cm H2O) than those with no or mild lung injury (5 cm H2O in both groups), as well as increased variability in PEEP measurements as compared to other groups. Tidal volumes were lower among severe lung injury observations as compared to those with less advanced forms of lung injury (median 450 vs. 500 mL); and FiO2 appeared to be higher, with interquartile ranges from 0.8 to 1.0 as compared to 0.4–0.6 in the other groups. As expected, there appeared to be a smaller proportion of observations with normal lung compliance (>40 ml/cm H2O) in this subgroup (54.9 %) compared to observations with no lung injury (87.6 %), mild lung injury (73.0 %), and moderate lung injury (67.1 %). Oxygenation, defined by both the median PaO2 and oxygenation index (OI), was lower for observations with severe lung injury compared to those without lung injury (PaO2: 69 vs. 167 mmHg; OI: 15.8 vs. 2.1).
Mean arterial blood pressure was found to be lower among observations with severe lung injury (median 82, IQR 75–92 mmHg) than in the other lung injury strata (IQR 78–103 for all observations; Table 2).
When assessing intracranial hemodynamics among the varying categories of lung injury, the median ICP was rather similar across all observations, while the cerebral perfusion pressure was lower in the severe lung injury group (median 70 mmHg) than the values obtained in all other groups (74, 75, and 81 mmHg for moderate, mild, and no lung injury, respectively; Table 3). With regard to therapy provided to patients, a greater percentage of data points with severe lung injury received hyperotonic saline therapy (15.0 %) and vasopressors (57.0 %) as compared to their moderate (12.9 and 38.5 %), mild (12.6 and 35.3 %), and no lung injury (6.3 and 17.3 %) counterparts. Similar percentages of observations in each stratum of the cohort were administered mannitol (Table 3).
Figure 2 displays the crude, unadjusted analysis of the relationship between PEEP and ICP, stratified by severity of lung injury. Results from the unadjusted analysis are given in Table 4, accounting for the correlation between an individual patient’s repeated observation. Univariate analyses indicated that for every centimeter H2O increase in PEEP, patients with no acute lung injury experienced an increase of 0.14 mmHg in ICP (p = 0.05), which compares to 0.08 mmHg (p = 0.26) in patients with mild lung injury, 0.12 mmHg (p = 0.04) in moderate lung injury, and 0.33 mmHg (p = 0.01) in severe lung injury. After adjusting for tidal volume, min volume, respiratory rate, peak inspiratory pressure, mean arterial blood pressure, PaCO2, and administration of vasopressors or hyperosmolar therapy, a significant relationship between PEEP and ICP persisted only in the severe lung injury group (p = 0.04). In this patient cohort, for every centimeter H2O increase in PEEP, there was a statistically significant increase in ICP of 0.31 mmHg (95 % CI [0.07, 0.54]).
A similar observation was made when looking at the relationship between PEEP and CPP (Fig. 3; Table 5). Results from both the univariate and multivariate models indicate a significant relationship in the severe lung injury group (p ≤ 0.02); however, no association was found in the moderate, mild, or no lung injury strata. After adjusting for relevant confounders (pH, tidal volume, min volume, respiratory rate, peak inspiratory pressure, and administration of vasopressors or hyperosmolar therapy), application of one centimeter of H2O of PEEP resulted in a 0.85 mmHg (95 % CI [−1.48, −0.22]) decrease in CPP.