We included all adult (>18 years old) patients admitted to our 50-bed surgical intensive care unit (ICU) with SAH from March 2004 until November 2010. Patients were identified retrospectively using codes from the International Classification of Diseases-10 (ICD-10).
Ethics, consent, and permissions
The study was approved by the institutional review board of Friedrich Schiller University Hospital, Jena, Germany (Bachstrasse 18, 07743 Jena). Informed consent was waived due to the retrospective, anonymous nature of the analysis.
Data collection
Two investigators (LM and PD) reviewed the medical charts and computed tomography (CT) images of patients with SAH during the study period. The Hunt and Hess score [9] (Additional file 1: Table S1), recorded prospectively by the referring physician at the onset of symptoms, was noted. The World Federation of Neurological Surgeons clinical grading scale (WFNS) [10] was calculated retrospectively using the initial Glasgow Coma Scale (GCS) score [11]. The extent of the SAH was graded according to the Fisher scale [12] (Additional file 1: Table S1), which assesses the amount of bleeding seen on the initial head CT scan. Complications related to SAH were also recorded and included the occurrence of vasospasm, hydrocephalus, and cerebral infarction (confirmed by CT imaging).
Physiologic, hemodynamic, and therapeutic data from the ICU stay were collected and automatically recorded by a patient data management system (Copra System GmbH, Sasbachwalden, Germany). Data recorded prospectively on admission included age, sex, primary and secondary admission diagnoses, and surgical procedures. The Simplified Acute Physiology Score (SAPS) II [13] was calculated on admission, and the Sequential Organ Failure Assessment (SOFA) score [14] was calculated daily by the physician in charge of the patient using a special sheet. In sedated patients, the GCS measured prior to initiation of sedation was considered.
Management of patients with SAH
An initial cerebral CT scan was performed routinely in all patients on arrival to the emergency room, after hemodynamic stabilization. In patients with CT evidence of increased intracranial pressure (ICP), massive hemorrhage (Hunt and Hess grade 4), brain edema, and no possibility for appropriate neurologic assessment because of ongoing analgosedation or severe impairment of the conscious level (GCS < 8), extraventricular drains were surgically inserted. In some patients with massive brain edema or hemorrhage, craniectomy was performed. Cerebral angiography was performed in all patients within 12 h of admission to the hospital.
On admission to the ICU, blood samples were routinely drawn to obtain a complete blood picture, serum creatinine, blood urea, C-reactive protein, bilirubin levels, activated prothrombin time (aPTT), and serum electrolytes (sodium and potassium). These parameters were measured at least once daily thereafter (at 6:00 a.m.) during the ICU stay. Fluid intake (enteral and parenteral) and output (urinary output, drains, and gastrointestinal losses) were measured and recorded hourly in the electronic charts. Insensible water loss was estimated hourly by the nurse in charge of the patient according to body mass index, body temperature, and the presence of mechanical ventilation [15].
According to our standard operative procedures (SOPs), patients with SAH were kept with a head-elevated position of 30°–45° with the head aligned to the body axis to avoid venous congestion. Pressure transducers were placed at the level of the ears. Central venous pressure (CVP) was measured and recorded every 4 h in the neutral position. In mechanically ventilated patients, the minute volume was adjusted to keep PCO2 within the normocapnic range (4.7–6.0 kPa). Patients with external ventricular drains had continuous monitoring of ICP and cerebral perfusion pressure (CPP), which was displayed as the difference between mean arterial and ICP. Vasospasm was assessed using transcranial Doppler (TCD) on a daily basis and, if present, graded into mild (≥120 <160 cm/s), moderate (≥160 <200 cm/s), or severe (≥200 cm/s) according to the maximal flow in any vessel. A cerebral CT scan was performed routinely after each intervention if there was clinical suspicion of intracranial complications, or every 3 days during the first 2 weeks after hospital admission to guide therapy.
The mean arterial blood pressure target was 70–80 mmHg for the first 3 days after SAH or to maintain a CPP > 65 mmHg in patients with external ventricular drains. The target was set at a higher level after the third day to reach 80–90 mmHg in patients without evidence of vasospasm and between 90 and 100 mmHg in those with vasospasm for up to 2 weeks or until the vasospasm had resolved. These targets were achieved by the infusion of incremental doses of norepinephrine. In patients requiring high doses of norepinephrine (>0.4 µg/kg/min), additional boli of crystalloids were considered at the discretion of the attending physician.
The target for fluid administration was to keep the daily fluid balance at zero or slightly negative (500–1000 ml/day). This was achieved using infusion of balanced full-electrolyte infusions (E153™; Serumwerk Bernburg AG, Bernburg, Germany, or Jonosteril™; Fresenius Kabi GmbH, Bad Homburg, Germany) at a basic rate of 1000–1500 ml/day. Colloid solutions were additionally used in some patients when clinically indicated in the form of 6 % hydroxyethyl starch (130/0.4, Voluven™; Fresenius Kabi, Bad Homburg, Germany). Since June 30, 2005, 4 % gelatin solutions (Gelafusal™; Serumwerk Bernburg AG, Bernburg, Germany) have replaced hydroxyethyl starch as the colloid of choice in our institution. Synthetic colloids have been completely banned in our ICU since 2008.
Outcome assessment
Sepsis was defined as the presence of infection, documented or supposed, plus systemic manifestations of this infection, and severe sepsis was defined as sepsis with associated organ failure [16]. All patients who survived the initial hospital stay were routinely given follow-up appointments at the neurosurgery polyclinic at 3, 6, and 12 months after SAH at which the neurologic status was examined and documented. Nine patients were lost to follow-up, but we were able to contact their next-of-kin by telephone to obtain the necessary information about neurologic outcome. The Glasgow Outcome Score (GOS) [17] was calculated retrospectively according to the available data: grade 1, death; grade 2, persistent vegetative state; grade 3, severe disability; grade 4, moderate disability, somewhat disabled but still independent for daily life; and grade 5, good recovery, although minor neurologic or psychological deficits could be present. Patients were stratified as having a poor (GOS ≤ 3) or good (GOS 4–5) outcome at 3, 6, and 12 months.
Statistical analysis
Data were analyzed using SPSS 16.0 for windows (SPSS Inc, Chicago, IL, USA). Nonparametric tests of comparison were used for variables evaluated as not being normally distributed. Difference testing between groups was performed using Student’s t test, Mann–Whitney U test, Chi-square test, or Fisher’s exact test as appropriate. Analysis of variance (ANOVA) was used to assess differences between groups over time with a post hoc Mann–Whitney U test to assess the differences at each time point.
To define the possible factors associated with poor outcome in SAH, we performed multivariable logistic regression analyses, with poor outcome (GOS ≤ 3) at 3, 6, and 12 months after the SAH, as the dependent variable. The variables considered for this analysis were age, sex, SAPS II on admission to the ICU, the maximum degree of extracranial organ dysfunction/failure as assessed by the maximum SOFA subscores during the ICU stay, duration of mechanical ventilation, the initial WFNS and Hunt and Hess score, the Fisher score from the first CT scan following the onset of SAH, localization of the ruptured aneurysm, the type of primary intervention, the mean hemoglobin level and the lowest mean arterial blood pressure during the first week in the ICU, the occurrence of infection or severe sepsis during the ICU stay, the cumulative fluid balance and the maximum dose of norepinephrine within the first week in the ICU, the use of colloids during the ICU stay, the occurrence of complications (vasospasm, hydrocephalus, and cerebral infarction) during the ICU stay, and the maximum sodium concentration during the ICU stay. To reduce the number of covariates in the multivariable models, we adopted a forward, stepwise approach with entry and removal based on a univariate p value of 0.2. Collinearity between variables was excluded before modeling (R
2 > 0.6), and none of the covariates was colinear. A Hosmer and Lemeshow goodness-of-fit test was performed, and odds ratios (OR) with 95 % confidence intervals (CI) were computed.
All statistics were two tailed. A p value <0.05 was considered to be significant. Continuous variables are presented as mean ± standard deviation or median [25–75 % interquartile range (IQ)] and categorical variables as number and percentage, unless otherwise indicated.