Bi-frontal pneumocephalus is an independent risk factor for early postoperative agitation in adult patients admitted to intensive care unit after elective craniotomy for brain tumor: A prospective cohort study

Postoperative agitation frequently occurs after general anesthesia and may be associated with serious consequences. However, studies in neurosurgical patients have been inadequate. We aimed to investigate the incidence and risk factors for early postoperative agitation in patients after craniotomy, specifically focusing on the association between postoperative pneumocephalus and agitation. Adult intensive care unit admitted patients after elective craniotomy under general anesthesia were consecutively enrolled. Patients were assessed using the Sedation-Agitation Scale during the first 24 hours after operation. The patients were divided into two groups based on their maximal Sedation-Agitation Scale: the agitation (Sedation-Agitation Scale ≥ 5) and non-agitation groups (Sedation-Agitation Scale ≤ 4). Preoperative baseline data, intraoperative and intensive care unit admission data were recorded and analyzed. Each patient’s computed tomography scan obtained within six hours after operation was retrospectively reviewed. Modified Rankin Scale and hospital length of stay after the surgery were also collected. Of the 400 enrolled patients, agitation occurred in 13.0% (95% confidential interval: 9.7–16.3%). Body mass index, total intravenous anesthesia, intraoperative fluid intake, intraoperative bleeding and transfusion, consciousness after operation, endotracheal intubation kept at intensive care unit admission and mechanical ventilation, hyperglycemia without a history of diabetes, self-reported pain and postoperative bi-frontal pneumocephalus were used to build a multivariable model. Bi-frontal pneumocephalus and delayed extubation after the operation were identified as independent risk factors for postoperative agitation. After adjustment for confounding, postoperative agitation was independently associated with worse neurologic outcome (odd ratio: 5.4, 95% confidential interval: 1.1–28.9, P = 0.048). Our results showed that early postoperative agitation was prevalent among post-craniotomy patients and was associated with adverse outcomes. Improvements in clinical strategies relevant to bi-frontal pneumocephalus should be considered. Trial registration: ClinicalTrials.gov (NCT02318199).


Introduction
Background/rationale 2 Explain the scientific background and rationale for the investigation being reported 4 Postoperative agitation after general anesthesia has been reported to occur in 3.7 to 29 % of patients……Therefore, we conducted this prospective cohort study of adult patients who had undergone elective craniotomy for brain tumors.
Objectives 3 State specific objectives, including any prespecified hypotheses 5 We aimed to investigate the risk factors for agitation, specifically focusing on the association between postoperative pneumocephalus and agitation. The association of agitation with long-term outcomes was also analyzed.

Study design 4
Present key elements of study design early in the paper 6 The patients were divided into two groups based on their maximal SAS score: the agitation group (maximal SAS ≥ 5) and the non-agitation group (maximal SAS ≤ 4).

Variables 7
Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers.
Give diagnostic criteria, if applicable

9-12
Agitation assessment and definition Assessment of postoperative CT scans Data collection Data sources/ measurement 8* For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group

9-12
The patients were divided into two groups based on their maximal SAS score: the agitation group (maximal SAS ≥ 5) and the non-agitation group (maximal SAS ≤ 4).

Bias 9
Describe any efforts to address potential sources of bias 9-12 Two attending neuroradiologists who were blinded to agitation status retrospectively reviewed each patient's first postoperative CT scans……Two neuroradiologists independently reviewed the CT scans. Discrepancies were resolved by discussion until consensus was reached.
Study size 10 Explain how the study size was arrived at According to standard recommendations, 10 cases of interest (agitation) would be required……We anticipated an average incidence of agitation in the present cohort using data from previous reports (11%), and planned to enroll 400 cases to identify risk factors for postoperative agitation. (b) Describe any methods used to examine subgroups and interactions 12 The possible interaction between variables was analyzed.
(c) Explain how missing data were addressed 12 Missing data and loss to follow-up were documented.
(d) Cohort study-If applicable, explain how loss to follow-up was addressed

Case-control study-If applicable, explain how matching of cases and controls was addressed
Cross-sectional study-If applicable, describe analytical methods taking account of sampling strategy 12 Missing data and loss to follow-up were documented.
(e) Describe any sensitivity analyses 12 The Hosmer-Lemeshow test was used to determine whether the model fitted the data adequately well.  Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders 14-21 Follow-up data are shown in Table 6 Outcome data 15* Cohort study-Report numbers of outcome events or summary measures over time 26 Other analyses 17 Report other analyses done-eg analyses of subgroups and interactions, and sensitivity analyses 23 Thus, our patients represented a population that was at high-risk of postoperative agitation, and our results may limit the generalization to the entire population of patients undergoing craniotomy for brain tumors.

Participants
Thus, our patients represented a population that was at high-risk of postoperative agitation, and our results may limit the generalization to the entire population of patients undergoing craniotomy for brain tumors.

Other information
Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based In the submission window *Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies.
Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at www.strobe-statement.org.