Comparison of outcomes of neurosurgical operations performed before and during the COVID-19 pandemic: a matched cohort study

Objective

To determine how the first wave of the COVID-19 pandemic affected outcomes for all operatively managed neurosurgical patients, not only those positive for SARS-CoV-2.

Design

Matched cohort (pairwise method).

Setting

A single tertiary neurosurgical referral centre at a large UK Major Trauma Centre.

Participants

During the first COVID-19 wave, 231 neurosurgical cases were performed. These cases were matched to cases from 2019. Cases were matched for age (±10 years), primary pathology and surgical procedure. Cases were excluded from analysis if either the age could not be matched to within 10 years, or the primary pathology or procedure was too unique. After exclusions, 191 cases were included in final analysis

Outcome measures

Primary outcomes were 30-day mortality and postoperative pulmonary complications. Secondary outcomes included Glasgow Outcome Score (GOS) on discharge, length of stay (LoS), operative and anaesthetic times and grade of primary surgeon. An exploratory outcome was the SARS-CoV-2 status of patients.

Results

There was no significant difference between the pandemic and matched cohorts in 30-day mortality, pulmonary complications, discharge GOS, LoS, operative or anaesthetic times. There was a significant difference in the variation of grade of primary surgeon. Only 2.2% (n=5) of patients had a SARS-CoV-2 positive swab.

Conclusion

During the first UK wave of the COVID-19 pandemic, the mortality, morbidity and functional outcomes of operatively managed neurosurgical patients at University Hospitals Birmingham were not significantly affected compared with normal practice. The grade of primary surgeon was significantly more senior and adds to the growing body of evidence that demonstrates how the pandemic has negatively impacted UK surgical training. Mixing COVID-19 positive, unknown and negative cases did not significantly impact on outcomes and indicates that further research is required to support the implementation of evidence-based surgical pathways, such as COVID-light sites, throughout the next stage of the pandemic.

Methods
Study design

The study was undertaken at the Queen Elizabeth Hospital Birmingham (QEHB) as a single-centre, matched cohort study. The QEHB is the largest hospital within the University Hospitals Birmingham (UHB) Foundation Trust, is one of three regional adult neurosurgical units in the West Midlands and is responsible for a mixed urban and rural population.

Participants

Operations performed during the initial stage of the pandemic (19th March 2020 to 1st June 2020) were matched to pre-pandemic cases (11th March 2019 to 11th September 2019). The pandemic time period was chosen as this was the interval in which elective neurosurgery cases at UHB were cancelled and will be referred to as the “initial pandemic phase” from here onwards. Cases were matched in a pairwise fashion for age at time of procedure (+/- 10 years), primary pathology and procedure. Primary pathology included severity where appropriate; for example, poor grade subarachnoid haemorrhage (SAH) was matched with another SAH of equivalent poor grade. Procedure was also matched to site where significant; for example a left-sided frontal craniotomy was matched with another left-sided frontal craniotomy rather than a right-sided. Ward-based procedures such as lumbar drain and ICP bolt insertion were not included. Cases were deemed unmatchable and were excluded from analysis if either the age could not be matched to within 10 years or the primary pathology or procedure was too unique.

Procedures

Cases were identified by performing a search of the Galaxy electronic operating theatre system for all operations carried out under a neurosurgical consultant within the chosen time periods. Galaxy and the Prescribing Information and Communications System (PICS) were then used to collate relevant variables.

Demographic data included age and gender. Operative data included name of procedure, grade of primary surgeon and operative time points. Grade of surgeon was defined as junior Senior Registrar (SpR)(ST3-5 or equivalent), senior SpR (ST5-8 or equivalent), fellow or consultant. Pre-operative anaesthetic time was defined as time “into anaesthetic room” to “knife to skin”, operative time was defined as “knife to skin” to “skin closure” and post-operative anaesthetic time was defined as “skin closure” to time “into theatre recovery”.

Clinical data included length of hospital stay (LoS) in days, discharge Glasgow Outcome Score (GOS), (10) 30-day mortality, post-operative pulmonary complications and COVID-19 swab status. Swabs were deemed to be positive if SARS-Cov-2 RNA was detected by the standard RT-PCR laboratory test. 

Outcomes

PRIMARY OUTCOMES

30-day mortality
Post-operative pulmonary complication

Primary outcomes were designed to be comparable to the COVIDSurg study.  ADDIN EN.CITE.DATA (8) For 30-day mortality, day of surgery was treated as day 0. Post-operative pulmonary complication was defined as pneumonia, acute respiratory distress syndrome (ARDS), or unexpected postoperative ventilation (any episode of non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation after initial extubation after surgery; or patient could not be extubated as planned after surgery).

SECONDARY OUTCOMES

Discharge GOS (1-5)
Length of stay in hospital (days)
Grade of primary surgeon
Pre-operative and post-operative anaesthetic time (minutes)
Operative time (minutes)

The Glasgow Outcome Score is an objective, functional outcome score from 1-5. (11) Favourable GOS was defined as a score of 4 (moderate disability) or 5 (good recovery). Unfavourable GOS was defined as a score of 1 (dead), 2 (vegetative state) or 3 (severe disability).

EXPLORATORY OUTCOME

COVID-19 status both pre- and post-operatively and the clinical course of positive patients.

Statistical methods

The study was conducted and reported in line with STROBE guidelines for cohort studies. (12) Continuous data were tested for normal distribution prior to analysis. Parametric data are presented as mean with 95% CI, and the unpaired t test used to detect differences between groups. Non-parametric data are presented as median with IQR, and Mann-Whitney used to detect differences between groups. The X2 test was used for categorical data. Missing data points were removed from final analyses. Clinical significance was defined as p<0.05.

Analyses were performed using GraphPad Prism software version 8.4.3 for Windows.

**研究目的** 明确新型冠状病毒肺炎（COVID-19）大流行第一波疫情对所有接受手术治疗的神经外科患者结局的影响，而非仅针对新型冠状病毒（SARS-CoV-2）检测阳性患者。

**研究设计** 配对队列研究（两两配对法）。

**研究场景** 英国大型创伤中心下属的单中心三级神经外科转诊中心。

**研究对象** 第一波COVID-19疫情期间，共计完成231例神经外科手术病例。将上述病例与2019年的手术病例进行配对，配对标准包括年龄（±10岁）、原发病理类型及手术方式。若无法在10岁范围内匹配年龄，或原发病理类型、手术方式过于特殊，则将该病例排除出分析。最终纳入最终分析的病例共191例。

**结局指标** 主要结局指标为30天死亡率与术后肺部并发症。次要结局指标包括出院时格拉斯哥预后评分（Glasgow Outcome Score, GOS）、住院时长（length of stay, LoS）、手术与麻醉时长，以及主刀医师资质等级。探索性结局指标为患者的SARS-CoV-2感染状态。

**研究结果** 疫情组与配对对照组在30天死亡率、肺部并发症、出院时GOS评分、住院时长、手术及麻醉时长方面均无显著差异。但主刀医师资质等级的分布存在显著差异。仅2.2%（n=5）的患者SARS-CoV-2咽拭子检测结果为阳性。

**研究结论** 在英国第一波COVID-19大流行期间，伯明翰大学医院接受手术治疗的神经外科患者的死亡率、并发症发生率与功能结局与常规诊疗相比无显著差异。但本次研究中主刀医师资质等级显著更高，这进一步补充了现有证据，表明大流行对英国外科培训产生了负面影响。混合COVID-19阳性、未知感染状态与阴性患者的诊疗方案并未对结局产生显著影响，这提示在大流行后续阶段，仍需开展进一步研究以支持基于证据的外科诊疗路径（如"COVID轻模式"病区）的落地实施。

## 研究方法

### 研究设计
本研究为单中心配对队列研究，于伯明翰伊丽莎白女王医院（Queen Elizabeth Hospital Birmingham, QEHB）开展。QEHB是伯明翰大学医院国民保健信托基金会（University Hospitals Birmingham Foundation Trust, UHB）旗下规模最大的医院，同时是西米德兰兹郡三家成人神经外科诊疗中心之一，服务区域涵盖城市与农村混合人口。

### 研究对象
将疫情初始阶段（2020年3月19日至2020年6月1日）完成的手术病例与大流行前（2019年3月11日至2019年9月11日）的手术病例进行配对。选择该疫情时段的原因是UHB在此期间暂停了择期神经外科手术，下文将该时段称为“疫情初始阶段”。采用两两配对法，按照手术时年龄（±10岁）、原发病理类型及手术方式进行匹配。原发病理类型在适宜情况下需匹配严重程度，例如，高分级蛛网膜下腔出血（subarachnoid haemorrhage, SAH）需与同等级别的高分级SAH病例配对。手术部位也需匹配，例如左侧额叶开颅术仅与左侧额叶开颅术配对，而非右侧额叶开颅术。病房操作（如腰椎引流术、颅内压螺栓置入术）未纳入本研究。若无法在10岁范围内匹配年龄，或原发病理类型、手术方式过于特殊，则该病例被视为不可匹配，将被排除出分析。

### 数据收集流程
通过检索Galaxy电子手术室系统，筛选出指定时段内由神经外科顾问医师主刀的所有手术病例。随后通过Galaxy系统与处方信息与通信系统（Prescribing Information and Communications System, PICS）整理相关研究变量。

### 研究变量
1. **人口学变量**：年龄与性别。
2. **手术相关变量**：手术名称、主刀医师资质等级及各时段手术时长。主刀医师资质等级划分为：初级高级住院医师（Junior Specialty Registrar, SpR，ST3-5及同等资质）、高级高级住院医师（Senior SpR，ST5-8及同等资质）、专科进修医师（Fellow）及顾问医师（Consultant）。麻醉前时长定义为“进入麻醉室”至“手术刀切开皮肤”的时间；手术时长定义为“手术刀切开皮肤”至“皮肤缝合”的时间；术后麻醉时长定义为“皮肤缝合”至“转入麻醉恢复室”的时间。
3. **临床资料**：住院时长（单位：天，length of stay, LoS）、出院时格拉斯哥预后评分（Glasgow Outcome Score, GOS）^[10]、30天死亡率、术后肺部并发症及COVID-19咽拭子检测结果。若标准实时荧光定量反转录聚合酶链反应（RT-PCR）实验室检测检出SARS-CoV-2 RNA，则判定咽拭子检测结果为阳性。

### 结局指标
#### 主要结局指标
1. 30天死亡率
2. 术后肺部并发症
本研究的主要结局指标设计参考COVIDSurg研究^[8]。对于30天死亡率，以手术当日为第0天。术后肺部并发症定义为肺炎、急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS），或术后意外通气支持（包括术后首次拔管后出现的任何无创通气、有创通气或体外膜肺氧合支持事件；或术后无法按计划完成拔管）。

#### 次要结局指标
1. 出院时GOS评分（1~5分）
2. 住院时长（单位：天）
3. 主刀医师资质等级
4. 术前与术后麻醉时长（单位：分钟）
5. 手术时长（单位：分钟）
格拉斯哥预后评分是1~5分的客观功能结局评分^[11]。良好预后定义为GOS评分4分（中度残疾）或5分（恢复良好）；不良预后定义为GOS评分1分（死亡）、2分（植物状态）或3分（重度残疾）。

#### 探索性结局指标
术前与术后COVID-19感染状态，以及阳性患者的临床病程。

### 统计学方法
本研究的实施与报告遵循加强流行病学观察性研究报告（STROBE）指南^[12]。分析前先对连续数据进行正态分布检验。符合正态分布的计量资料以均数±95%置信区间（95% CI）表示，采用独立样本t检验比较组间差异；不符合正态分布的计量资料以中位数（四分位数间距，IQR）表示，采用曼-惠特尼U检验比较组间差异。分类资料采用卡方检验进行分析。最终分析中剔除存在缺失数据的病例。以P<0.05作为具有临床统计学意义的阈值。
所有数据分析采用Windows版GraphPad Prism 8.4.3软件完成。