Safety and Effectiveness of an Enhanced Recovery Protocol in Patients Undergoing Burr Hole Evacuation for Chronic Subdural Hematoma

BACKGROUND AND OBJECTIVES: Enhanced recovery programs may be especially useful in patients with chronic subdural hematoma or hygroma (cSDH), who frequently exhibit frailty and multimorbidity. We aim to evaluate the real-world safety and effectiveness of an enhanced recovery protocol in this population. METHODS: From a prospective registry, burr hole evacuations for cSDH carried out under the protocol (including early thromboprophylaxis, no flat bed rest, early mobilization without drain clamping, and early resumption of antithrombotic medication) were extracted, along with those procedures carried out within the past year before protocol change. Propensity score–based matching was carried out. A range of clinical and imaging outcomes were analyzed, including modified Rankin Scale as effectiveness and Clavien–Dindo adverse event grading as safety primary end points. RESULTS: Per group, 91 procedures were analyzed. At discharge, there was no significant difference in the modified Rankin Scale among the standard and enhanced recovery groups (1 [1; 2] vs 1 [1; 3], P = .552), or in Clavien–Dindo adverse event grading classifications of adverse events (P = .282) or occurrence of any adverse events (15.4% vs 20.9%, P = .442). There were no significant differences in time to drain removal (2.00 [2.00; 2.00] vs 2.00 [1.25; 2.00] days, P = .058), time from procedure to discharge (4.0 [3.0; 6.0] vs 4.0 [3.0; 6.0] days, P = .201), or total hospital length of stay (6.0 [5.0; 9.0] vs 5.0 [4.0; 8.0] days, P = .113). All-cause mortality was similar in both groups (8.8% vs 4.4%, P = .289), as was discharge disposition (P = .192). Other clinical and imaging outcomes were similar too (all P > .05). CONCLUSION: In a matched cohort study comparing perioperative standard of care with a novel enhanced recovery protocol focusing on evidence-based drainage, mobilization, and thromboprophylaxis regimens as well as changes to the standardized reuptake of oral anticoagulants and antiaggregants, no differences in safety or effectiveness were observed after burr hole evacuation of cSDH.


Patient blood management
In cases of anemia: for elective procedures according to institutional patient blood management protocol 27 In cases of anemia: for elective procedures according to institutional patient blood management protocol 27  usually consist of a range of multidisciplinary, evidence-based elements that reach from optimization of a patient's health state up to reducing the physiological burden of the surgery itself and improving the postoperative rehabilitation process.][7][8] In October 2022, we implemented a novel institutional protocol (Table 1) implementing several ERAS elements, governing the preoperative, perioperative, and postoperative care of patients undergoing surgery for cSDH.Although some ERAS elementssuch as patient blood management-had already been implemented before in our previous, "standard protocol," the changes to this protocol focus on evidence-based drainage, mobilization, and thromboprophylaxis regimens as well as changes to the standardized reuptake of oral anticoagulants and antiaggregants.Therefore, the aim of this study is to evaluate the safety and effectiveness-thus the real-world impact-of implementing an enhanced recovery protocol for burr hole evacuation of cSDH in a propensity-matched cohort study based on our prospective institutional registry.

Overview and Data Collection
Our institutional protocol was changed from the previous "standard protocol" to the novel ERAS protocol and implemented from October 3rd, 2022, onward.To evaluate the real-world safety and effectiveness of the protocol, we analyze all adult patients who have undergone burr hole surgery for subdural chronic hematoma or hygroma at the Department of Neurosurgery of the University Hospital Zurich, from October 3rd, 2022, up to June 2023, as this allowed these patients to complete the 6-week follow-up visit.We excluded procedures done for subdural empyema/abscesses or those primarily planned as craniotomies (Figure 1).We then extracted data for all patients undergoing the same procedure-under the "standard protocol"-during the preceding year, thus from October 2021 up to October 2022.To increase the comparability of the 2 cohorts, propensity score-based matching is carried out.All analyses are performed under the intention-to-treat (ITT) principle.Thus, all eligible patients operated within the active time frame of the "standard" or the novel protocol are analyzed in that group-regardless of whether any or all of the elements were actually implemented for that specific patient.Data extraction is based on our prospective institutional patient registry, which collects demographic, procedural, adverse events, and clinical outcome data.Missing data and imaging or anticoagulant/antiaggregant data are retrospectively added.Oral anticoagulants or antiaggregants are restarted 1 day after removal of sutures/staples [19][20][21][22][23][24] ERAS, enhanced recovery after surgery; I.U., international units; i.v., intravenous; s.c., subcutaneous.Ethical approval was obtained for our research registry (KEK-ZH-PB-2017-00093).All patients consented to research use of their data.

Interventions Protocols
0][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Major differences are as follows: 1. Thromboprophylaxis is started 6 hours postoperatively, instead of after 48 hours after drain removal 2. Patients postoperatively rest with the upper body 30°elevated, instead of in flat supine position 3.After 6 hours, patients are allowed to sit up and mobilize, instead of strict bed rest until drain removal 4. When sitting up or mobilizing, the drain does not need to be clamped, instead of it having to be clamped shut before 5.The drainage bag is generally held at heart level, instead of fixated to the bed at neck or shoulder level 6.Oral anticoagulants and antiaggregants are started again 1 day after suture/staple removal (which is done on postoperative day 8), instead of only after the clinical follow-up visit 4-8 weeks after surgery

Surgical Technique
The patient is positioned in supine or semilateral position with the upper body and head slightly elevated and turned so that the frontal burr hole corresponds to the highest point of the head.For bilateral procedures, the patient is positioned supine with the head on a half-moon headrest.The Stephanion and parietal tuberosity are identified, and short skin incisions made over each.After dissecting the periosteum, 14-mm burr holes are placed over the Stephanion and the parietal tuberosity.Hemostasis is achieved using bone wax.The dura is incised in a cruciform fashion and coagulated, first frontally and then parietally.Ringer's solution at body temperature is flushed from both burr holes until good communication is achieved between the 2 and until the solution flows back clearly.A Redon drainage is then placed subperiosteally, covering both burr holes.The parietal incision is then closed with inverted galeal sutures and the skin closed with staples.Finally, the remaining subdural space is filled with Ringer's solution until no air remains subdurally, and the frontal incision is closed in the same fashion.

Outcome Measures Baseline Characteristics
Apart from basic demographic characteristics, we collected American Society of Anesthesiologists scores, emergency vs elective procedures, presence of subdural hematoma vs hygroma, unilateral or bilateral  surgery, conversion to craniotomy, previous surgery for cSDH, surgical time in minutes, preoperative epileptic episodes, and preoperative presence of anticoagulants such as vitamin K inhibitors or direct FXa inhibitors, as well as antiaggregants such as acetylsalicylic acid or ADP/ P2Y inhibitors.

Primary End Points
The primary safety end point (both measured at discharge) was defined as any adverse event as graded by the Clavien-Dindo (CDG) classification, 27 while the primary effectiveness end point was defined as functionalneurological outcome as graded by the modified Rankin Scale (mRS).

Secondary End Points
As secondary clinical outcomes, we collected Glasgow Coma Scale (GCS), Karnofsky Performance Status (KPS), and National Institutes of Health Stroke Scale as well as presence of focal sensorimotor deficits and all-cause mortality up to first follow-up.In cases of mortality, we defined mRS as 6, KPS as 0, GCS as 3, and CDG as V.We also recorded time up to drain removal, time from procedure to discharge, and total length of hospital stay in days.Discharge disposition was also recorded.Finally, in terms of imaging outcomes, we recorded absolute and dynamic evacuation results on noncontrast computed tomography (CT) at first follow-up, once as an absolute classification (complete resorption/residual  hematoma ≤2 mm or ≥2 mm/unchanged or increased thickness), and once as a comparison to preoperative imaging (complete resorption or decrease/unchanged thickness/increased thickness).For both measurements, the maximum residual thickness of the hematoma was measured.
In cases of bilateral surgery, the thicker residual was counted.

Statistical Analysis
Categorical variables are reported as numbers (percentages).Distribution of continuous variables is checked using histograms; all are found not to be approximately normally distributed.Continuous data are reported as medians IQRs.Analyses are carried out per procedure-not per patient-and group assignment according to the ITT principle.All eligible patients are pooled, and 2 optimal groups are constructed in a 1:1 ratio using nearest-neighbor propensity score-based matching 28 for sex, age, emergency surgery, bilateral or unilateral surgery, GCS at admission, presence of hematoma vs hygroma, intake of anticoagulant drugs, and presence of preoperative epileptic events.An overview of prematching data is provided in Supplemental Digital Content 1, Tables 1-3 (http:// links.lww.com/NEU/E104).No imputation was carried out.Intergroup comparisons were then made using Mann-Whitney U tests for continuous and ordinal, as well as Pearson's χ 2 tests for categorical variables.All analyses were performed using version 4.3.1 of R (R Foundation for Statistical Computing; https://www.R-project.org/). 29A 2-tailed P ≤ .05 was considered statistically significant.

RESULTS
Data on a total of 209 eligible procedures were available (Figure 1), of which 118 in the standard and 91 in the enhanced recovery protocol group.After matching, 91 procedures were available per group.Table 2 provides an overview of baseline characteristics, without evidence of differential distribution among the 2 groups, apart from median surgical time, which was significantly longer in the standard protocol vs the enhanced recovery group (57.0 [45.0; 70.0] vs 45.0 [36.0; 60.0] minutes, P < .001).Overall, 3.3% of procedures were carried out under local anesthesia, without significant intergroup difference (5.5% vs 1.1%, P = .213).Data on clinical first follow-up were lost for 16 procedures (8.8%), and the median length of follow-up in weeks was 6 [5; 8].Primary end point results are illustrated in Figure 2.

Safety-Adverse Events
At discharge, there was no significant difference in CDG classifications of adverse events (P = .282,Table 4) or in the occurrence of any adverse events (15.4% vs 20.9%, P = .442).Similar results were observed at follow-up for CDG classifications (P = .444)or occurrence of any adverse events (34.1% vs 35.2%, P = .560).

DISCUSSION
In this matched comparison of an enhanced recovery protocol for burr hole evacuation of cSDH vs its standard predecessor based on a prospective single-center registry, there was no evidence for superiority or inferiority of the novel protocol in terms of safety or effectiveness.
Strategies to improve recovery after surgery have not only demonstrated their benefits in various specialties, including in spinal and-to a lesser extent-also in cranial neurosurgery, but they may be of particular importance in those patient populations who show high levels of frailty and multimorbidity, and thus are more prone to hospital-acquired adverse events. 5,8Patients with cSDH fit this description relatively well, and there is very limited evidence on such strategies in this specific group of patients. 1One crucial characteristic of the ERAS concept is that each intervention that is implemented as an element within a protocol must be at least somewhat evidence-based.Although there are as of yet no published ERAS protocols for burr hole evacuation of cSDH, some evidence on specific interventions that could be combined into a multimodal protocol does exist.
In our protocol, we start thromboprophylaxis using heparin 6 hours postoperatively, whereas we would only do so after 48 hours in our previous protocol.This decision was based on the retrospective single-center study by Licci et al, 16 which demonstrated no difference in the recurrence rate after evacuation of cSDH whether thromboprophylaxis was started before or after 48 hours.Their study, however, did find a correlation of increased doses of thromboprophylaxis leading to increased recurrence rates.Our data corroborate these findings, demonstrating no difference in imaging or clinical outcomes regardless of administration time point.However, there was also no clear benefit in starting thromboprophylaxis earlier, as complication rates-including thromboses-were also unchanged.Nonetheless, it appears safe to start a heparin drip 6 hours postoperatively.
The protocol also allowed a 30°upper-body elevation as opposed to flat bed rest, and allowed early mobilization after 6 hours as opposed to strict bed rest until drain removal.A multicenter prospective study by Brennan et al 13 demonstrated that postoperative bed was an independent predictor of unfavorable functional outcome, while Kurabe et al 14 show that upright positioning and mobilization on the same day as surgery led to decreased complications while maintaining the same recurrence rate in a retrospective single-center study.The randomized controlled trial (RCT) by Nakajima et al 30 demonstrated no effect of postoperative posture on recurrence, while the RCT by Abouzari et al 31 saw a slight increase in recurrence rates with upright vs supine positioning.In addition, a meta-analysis of 4 studies by Zhu et al 15 found that postoperative bed header position (upright or flat) had no effect on recurrence rates.These previous studies fit well with our observations and in summary indicate that it is likely safe to allow patients to sit in an upright position and to mobilize patients on the day of surgery.
Furthermore, the novel protocol specified that oral anticoagulant and antiaggregant drugs ought to be started 1 day after suture/staple removal-thus usually on the ninth postoperative day and after early wound complications that might require revision are ruled out-as opposed to only after a 4-to 8-week clinical visit with noncontrast CT imaging.9][20][21][22][23] For example, Fornebo et al 19 carried out a retrospective study of 763 patients and found that recurrence rates were not significantly different between early vs late (≤30 vs >30 days) resumption of anticoagulants or antiaggregants, but that the late resumption group did have significantly more thromboembolic complications.Retrospective studies by Amano et al 18 and Guha et al 32 demonstrate that-in this population-severe thromboembolic events occur usually within the first month after surgery, especially in those patients who were on anticoagulant drugs before cSDH evacuation.The latter of the 2 also provides some evidence that it is safe to restart anticoagulants and antiaggregants at 3 days postoperatively. 32A meta-analysis by Phan et al 21 demonstrated no difference in hemorrhagic complications when resuming antithrombotic agents in <2 weeks vs >1 month, while earlier resumption did lead to significantly lower thromboembolic complications.
These data show that implementing our protocol-at least in its earliest stages of adoption-did not affect adverse events or any type of outcome, neither positively nor negatively.Of course, it has to be considered that "soft" outcomes such as patient comfort and satisfaction are not considered here, or that adherence to the protocol elements in truth was perhaps lower than expected in these first months of adoption, as adherence usually increases over time. 7,33It is also noteworthy that length of stay and discharge disposition-2 further important outcomes concerning ERAS-were unchanged.One potential reason that impact was low here could be inherent to the Swiss health system.The threshold for referral to a rehabilitation clinic is low and postoperative waiting times for a bed in a rehabilitation clinic are long.Thus, a large proportion of patients with neurocognitive or focal deficits are either sent to rehabilitation after a prolonged hospital stay, or are transferred to regional hospitals, to wait for a rehabilitation bed there.
It still is difficult to find appropriate, high-level evidence for each single element of clinical care, such as how many days exactly one should wait until resuming antithrombotic drugs, or what height exactly the drainage bag should be fixed to.Likely, it will also remain impossible to ever generate such high-level evidence for any such decision, using RCTs or large, multicenter, prospective studies.This is one of the reasons why much of ERAS research-and inherently so, surgical science in general-must also rely to a certain extent on pragmatic studies reporting the realworld experience of a surgical team with a protocol that is as clearly defined and as standardized as it is possible in actual clinical practice.Such studies aiming to evaluate the effectiveness 34 (thus, the real-world performance of an intervention in a broad patient group) can still be crucial in guiding surgical management, which cannot always be represented in studies aiming to evaluate efficacy (thus, the performance of an intervention under research circumstances, such as in a RCT with narrowly defined inclusion and exclusion criteria).
Although our data provide some evidence on a novel enhanced recovery protocol for patients undergoing evacuation of cSDH, further prospective, multicenter studies with larger samples are required to validate the safety and effectiveness of our protocol with a higher level of evidence.In addition, RCTs could provide a high level of evidence regarding its efficacy and are probably necessary before such protocols can be more widely adopted clinically.It will also be crucial to validate novel elements that can then be added to protocols, then finally also comparing different protocols with each other.

Limitations
The most important limitation of this study is the lack of an analysis of protocol adherence.It is known that the most important factor determining the impact of ERAS protocols is the percentage of adherence to the single ERAS elements. 33It is likely that not all elements have been strictly adhered to in each patient, and it is possible that subsets of patients with higher adherence might demonstrate improved outcomes.Furthermore, we used propensity score-based matching to increase the comparability of the 2 study groups.However, matching can only account for confounders that are collected and indeed matched for, in contrast to, eg, a randomized study design that equally distributes all confounders.In addition, it was necessary to supplement some data retrospectively, such as imaging results and antiaggregant/ anticoagulant drug intake.Still, the majority of outcomesimportantly including our primary end points-were prospectively collected.It is known that especially regarding complications, prospective registries tend to result in significantly higher complication rates than retrospective analysis of adverse events.Our study is also not powered to demonstrate numerically small but potentially clinically important differences, which would require a far larger number of included patients.

CONCLUSION
In a matched cohort study comparing perioperative standard of care with a novel enhanced recovery protocol focusing on evidence-based drainage, mobilization, and thromboprophylaxis regimens as well as changes to the standardized reuptake of oral anticoagulants and antiaggregants, no differences in safety or effectiveness were observed after burr hole evacuation of cSDH.

FIGURE 1 .
FIGURE 1. Flowchart demonstrating the flow of procedures collected in the prospective institutional registry up to statistical analysis.ERAS, enhanced recovery after surgery.

FIGURE 2 .
FIGURE 2. Grotta bar charts demonstrating A, the primary effectiveness (functional-neurological outcome as graded by the modified Rankin Scale) and B, safety (adverse events as graded by the classification described by Clavien and Dindo) at discharge and at first follow-up.ERAS, enhanced recovery after surgery; mRS, modified Rankin Scale.

TABLE 1 .
Overview of the Standard Protocol and the Subsequently Implemented ERAS Protocol neurosurgery-online.com CLINICAL RESEARCH

TABLE 3 .
Summary of Clinical Outcome Data at Admission, Discharge, and First Follow-up ERAS, enhanced recovery after surgery; GCS, Glasgow Coma Scale; mRS, modified Rankin Scale; KPS, Karnofsky Performance Status; NIHSS, National Institutes of Health Stroke Scale.

TABLE 4 .
Summary of Adverse Events (at Discharge and at First Follow-up) as Well as Imaging Outcomes (at First Follow-up) on Computed Tomography ERAS, enhanced recovery after surgery.a Compared with baseline imaging.