key: cord-0889499-q8aod1a5 authors: Alam, Intekhab; Garg, Kanwaljeet; Raheja, Amol; Tandon, Vivek; Sharma, Ravi; Singh, Manmohan; Singh, Gyaninder Pal; Mishra, Shashwat; Singh, Pankaj Kumar; Agarwal, Deepak; Soni, Kapil Dev; Suri, Ashish; Chandra, Poodipedi Sarat; Kale, Shashank Sharad title: Managing Traumatic Brain Injury during the COVID-19 pandemic- A Case Matched Controlled Analysis of Immediate Outcomes date: 2022-05-25 journal: World Neurosurg DOI: 10.1016/j.wneu.2022.05.076 sha: 1babbe3f229d4a6535ec7910702f5f2686452e09 doc_id: 889499 cord_uid: q8aod1a5 Objective The primary objective of this study was to evaluate the outcome of traumatic brain injury (TBI) patients during the COVID-19 pandemic and to compare their outcome with case matched controls from the pre-pandemic phase. Methods This is a retrospective case-control study in which all TBI patients admitted during COVID-19 pandemic phase (Arm-A) from 24th March, 2020 till 30th November, 2020 were matched with age and Glasgow Coma Scale score matched controls from the patients admitted prior to March 2020 (Arm-B). Results The total number of patients matched in each arm was 118. The length of hospital stay (8 days versus 5 days, p<0.001), transit time from emergency room to operation room (150 minutes versus 97 minutes, p=0.271), anesthesia induction time (75 minutes versus 45 minutes, p=0.002) and operative duration (275 minutes versus 180 minutes, p=0.002) were longer in Arm-A. Although the incidence of fever and pneumonia were significantly higher in Arm-A than Arm-B (50% versus 26.3%, p<0.001 and 27.1% versus 1.7%, p<0.001, respectively), outcome (GOS-E) and mortality rates (18.6% versus 14.4% respectively, p=0.42) were similar in both the groups. Conclusion The outcome of the patients managed for TBI during the COVID-19 pandemic was similar to matched patients with TBI managed at our center before the onset of COVID-19 pandemic. This suggests that the guidelines followed during the COVID-19 pandemic were effective in dealing with TBI patients. This model can serve as a guide for any future pandemic waves for effective management of TBI patients without compromising their outcome. First case of COVID-19 was reported from Wuhan, China on 31st December 2019 1 . Rapid spread of this highly contagious disease led to unprecedented challenges in healthcare delivery right across the world. COVID-19 has also disrupted the care of traumatic brain injury (TBI) patients, as it has affected the other subspecialities in neurosurgery. Clinical decision-making process in TBI patients with COVID-19 positive status is further complicated by overlapping clinical, radiological and biochemical profiles. Concomitant elevation of serum inflammatory markers, neurogenic pulmonary edema, and ventilatory support often required in obtunded TBI patients are some of the cardinal features seen in head injury patients, which can mimic observations seen in severe COVID-19 infection. Many studies have highlighted this aspect 2 . To control the COVID-19 pandemic in India, a nationwide lockdown was enforced on 24th March 2020. During the nationwide lockdown, it was quickly realized that the patients with TBI and the treating neurosurgeons encountered unique challenges. We undertook this retrospective casecontrol study, where patients of TBI treated during the first wave of pandemic, when vaccine was not available, were compared with matched [age, radiological diagnosis and Glasgow Coma Scale (GCS) score equivalent] controls with TBI who were treated before the onset of COVID-19 pandemic and nationwide lockdown at our tertiary care referral center. The objective of the study was to understand the impact of COVID-19 on the treatment and outcomes of patients with TBI and ascertain the factors predicting outcome. We have also formulated guidelines for the management of TBI patients based on our experience and pertinent studies from the literature. These guidelines can be useful in the future, in case there is a resurgence in the number of COVID-19 cases. Though there has been abundance of articles describing the perceptions of neurosurgeons and guidelines to manage TBI patients during COVID-19 pandemic, not many articles have compared the outcomes of TBI patients managed during COVID-19 pandemic with those managed before the onset of COVID-19 pandemic [3] [4] [5] . The data presented in this article presents the results of a 'test of the guidelines' followed at our center during the pandemic. This retrospective case-control study included patients with TBI managed at a tertiary care referral center dedicated to trauma care in northern India with a large catchment area. Patients in Arm-A (cases) included TBI patients admitted between 24th March 2020 to 30th November 2020 (during the first wave of COVID-19 pandemic) while Arm-B (controls) included TBI patients managed before 31st December 2019. The study was conducted after obtaining the required ethical clearance (IEC PG-257/24.06.2020). Following inclusion and exclusion criteria were used to select patients for our study-All consecutively managed patients of TBI after the onset of COVID-19 pandemic from 24th March 2020 to 30th November, 2020 were included (Arm-A). Patients with incomplete records, those who had follow-up less than 6 months, concomitant spinal injury, prior surgery, pregnancy or previous head injury were excluded. Arm-B consisted of case-matched TBI patients (controls), who were managed at our center for TBI before 31st December 2019. Matching was done in a 1:1 ratio for age, GCS score, and radiological diagnosis. For matching of age, the exact number in years was matched in patients of both Arm-A and Arm-B. For patients with age <18 years, exact matching of age in years was done. Similarly exact matching for GCS (Eye/Verbal/Motor) scores was done for patients in both arms. For matching of radiological diagnosis, TBI patients were categorized based on most pertinent finding on NCCT head and matched, i.e., SDH with SDH, EDH with EDH, and so on. the early phase of pandemic, i.e., 24th March-31st July 2020 and late phase of the pandemic, i.e., 1st August-30th November 2020 and their outcomes assessed. Computerized patient database of our hospital was used to retrieve demographic, clinical, management and outcome data of the selected cases. Statistical analysis was done using SPSS (Statistical Package for the Social Sciences) version 26 and R language v 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria). Categorical data is expressed as percentage while continuous data are expressed as mean with standard deviation. Categorical data were analyzed using the Chi-Square test or Fisher's exact test, wherever indicated. Continuous data were tested using the student's t-test or ANOVA if the data met the condition of normality for these tests, otherwise non-parametric counterparts were used. Multivariate logistic regression analysis was run to ascertain factors predicting outcome. A total of 341 patients were managed with a diagnosis of traumatic cranio-spinal injuries at our center during the study period. This number was significantly less as compared to the number of cases of craniospinal trauma managed at our center during the same time period in 2018 (n = 1302) and 2019 (n = 1246). 118 patients met the inclusion criteria and were included in Arm-A of our study. (Figure 1 ). Similar number of matched controls (n=118) were selected as per the methodology described above and were included in Arm-B. The patients in both arms were comparable in terms of gender, mode of injury, place of injury and co-morbidities (p>0.05) ( Table 1) . The mean age of the patients in Arm-A and B was 31.8± 20.1 years and 32.1± 20.2 years (p -0.354), respectively (Table 1) . Road traffic accidents (high velocity trauma) was the predominant J o u r n a l P r e -p r o o f mode of injury in both arms. There were 29 (24.6%) COVID-19 positive patients in Arm-A. Median GCS was 14 (range 12) in both groups. 33.9% of patients had severe head injury, 54.2% of patients had minor head injury while 11.9% of patients had moderate head injury in Arm-A, and the numbers were similar in the matched Arm-B. Contusion (35.6%) was the most common radiological diagnosis in both arms. Thirty-one (26.2%) patients required surgical intervention in Arm-A while 40 (33.9%) patients required surgical intervention in Arm-B (p -0.188). All acute SDH and patients with intracerebral bleed, requiring surgical intervention, underwent traditional, unilateral decompressive craniectomy with hematoma evacuation and lax duraplasty. Patients with EDH underwent hematoma evacuation. Patients with contusion underwent unilateral Frontoparieto-temporal decompressive craniectomy and lax duroplasty. The median GOS-E at discharge was similar in both the arms (GOS-E 8 in Arm-A versus GOS-E 8 Arm-B, p -0.557) as was the mortality rate . Median GCS at the time of discharge was 15 in both the arms (p -0.095). The incidence of fever and pneumonia was statistically significantly higher in the patients in Arm-A as compared to those in Arm-B [50% versus 26.3% (p <0.001) and 27.1% vs 1.7% (p <0.001), respectively]. The mortality rate of severe TBI patients was 40% (n = 16) and 30% (n = 12) in Arm-A and B, respectively (p -0.238). The demography of COVID-19 positive TBI patients, including mode of injury, place of injury and co-morbidities in Arm-A were like their matched controls in Arm-B. The median time needed for induction during operation and the total operative time was significantly longer in the COVID-J o u r n a l P r e -p r o o f 19 positive TBI patients in Arm-A as compared with their matched controls in Arm-B (60 mins versus 27.7 mins, p -0.032 and 300 mins versus 130 mins, p -0.016, respectively) ( Table 2 ). The median length of hospital stays of COVID-19 positive TBI patients in Arm-A was significantly longer than their matched controls in Arm-B (12 days versus 4 days, p <0.001). The incidence of fever and pneumonia was higher in Arm-A than in Arm-B (65.5% versus 24.1%, p -0.002 and 96.6% versus 6.9%, p -<0.001, respectively). The median GOS-E at discharge in Arm-A and Arm-B was 7 and 8, respectively (p -0.113) with the median GCS at discharge of 15 in both the groups (p -0.141). The mortality in COVID-19 positive patients in Arm-A was 27.6% and in Arm-B was 17.2% (p -0.375). COVID-19 positive patients in Arm-A were comparable to COVID-19 negative patients with respect to gender, mode of injury, place of injury and comorbidities. COVID-19 positive TBI patients were comparatively older than the COVID-19 negative patients in Arm-A (39.9 ± 18.0 years versus 29.2 ± 20.1 years, p=0.012). Time to shift TBI patients to ORs, time for induction, total operative time and final patient outcome was similar in the COVID-19 positive patients and COVID-19 negative patients in Arm-A (Table 3) . However, COVID-19 positive patients had a longer duration of hospital stay than COVID-19 negative patients (12 days versus 7 days, p=0.001). The TBI patients in the early phase of the pandemic were comparable with those in the later part of the pandemic with respect to age, gender and the treatment being given them (p >0.05). However, the median length of hospital stay of TBI patients was significantly longer in the initial phase of the pandemic when compared with the later phase (9 days versus 6 days, p -0.023) ( Table 4 ). The GOS-E at discharge, GCS at discharge and complications rate were similar during the early and the late phase of the pandemic (p > 0.05). J o u r n a l P r e -p r o o f On univariate analysis, longer hospitalization; midline shift > 5 mm; effaced sulci and gyri on NCCT head; larger size of hematoma (> 40 ml); severe TBI; fever, meningitis and ventilator associated pneumonia (VAP) during hospital stay were significantly associated with poor outcome (GOS-E <= 4) at the time of discharge. COVID-19 infection was not found to be an independent predictor of poor outcome on univariate analysis. On multivariate analysis, severe TBI and meningitis during hospital stay were found to be significant factors predicting poor outcome at discharge (Table 5 ). The World Health Organization (WHO) announced COVID-19 as a global pandemic on 12th March 2020 and many countries announced various measures including strict lockdowns to prevent transmission of the disease. At the peak of the pandemic in every country, healthcare facilities were overwhelmed because of the surge in COVID-19 positive cases. Medical facilities including ICU beds and doctors were diverted to manage COVID-19 patients. Many international centers reported the infrastructural changes done during COVID-19 pandemic to conform to the new guidelines 4, [7] [8] [9] . Management protocols were devised in many parts of the world to manage emergency cases including TBI to ensure consistent and high-quality healthcare delivery to non-COVID-19 patients [10] [11] [12] . Safeguarding non COVID-19 patients and healthcare workers from COVID-19's transmission was a big challenge. The recommendations of our hospital infection control committee (HICC) and other groups are summarized in Table 6 . Stay at home orders or lockdowns were enforced to contain the spread of this novel infection which resulted in decreased motor vehicular accidents. The decreased incidence of TBI, as appreciated at our center, has also been reported in literature during pandemic 13 . However, unlike many studies reported in literature we did not find any significant change in the mode of TBI, with RTA remaining the biggest contributor in our cohort. All TBI patients coming to the ER of our hospital were screened for risk of COVID-19 with a 'Checklist for COVID-19 suspicion' followed by CB-NAAT testing. Those patients who were J o u r n a l P r e -p r o o f negative for COVID-19 were managed as per the Brain Trauma foundation (BTF) guidelines. TBI patients who came positive for COVID-19 were shifted to COVID-19 designated facilities and were managed for COVID-19 apart from normal neurosurgical care. COVID-19 positive TBI patients were categorized into -1. Mild COVID-19/ Mild TBI, 2. Moderate COVID-19/ Moderate TBI and 3. Severe COVID-19/ Severe TBI based on GCS at admission, blood oxygen saturation (SpO2) on room air and respiratory rate. In the initial phase of the pandemic, mild COVID-19 patients were given Hydroxychloroquine, Ivermectin, Tetracycline, Zinc, and Vitamin C, as per the guidelines of the national task force [14] [15] [16] [17] . But with growing evidence of literature, we preferred only hydroxychloroquine or ivermectin for mild COVID-19 cases 18 . However, the recent literature does not support the use of hydroxychloroquine and ivermectin as a prophylaxis in patients with COVID-19 and we have stopped their usage in our clinical practice 19-21 . Remdesivir and Tocilizumab were reserved for moderate to severe cases of COVID-19, where the use of these drugs was indicated as per our protocol. Growing evidence on the role of steroids in COVID-19 management led to the addition of inhalational budesonide in the treatment protocol for mild COVID-19 cases and injectable methylprednisolone for moderate and severe cases 22 . All COVID-19 positive TBI patients were monitored serially with biomarkers of inflammation (IL-6, CRP, Ddimer, Procalcitonin) as and when required for seeing any rising trend. Figure 2 shows the present management protocol for COVID-19 positive TBI patients at our center. Due to closure of the trauma center, to avert acute shortage of beds, nearly one-third bed strength in the main neurosurgical center was dedicated for neurotrauma cases. All semi-elective surgeries like surgeries for brachial plexus injuries and cranioplasties were postponed. Testing and quarantine protocols were made for our department in sync with the hospital policies 23 . The logistic issues faced due to the new protocols gradually decreased, as is evident from the results shown in this study. The time needed to shift the patients from ED to OR decreased in the second phase as compared to phase 1. We observed that the length of hospital stay of TBI patients in Arm-A was significantly longer than in Arm-B. Moreover, the COVID-19 positive patients in Arm-A had statistically significantly longer length of hospital stay than their matched controls in Arm-B and COVID-19 negative patients in Arm-A. Thus, COVID-19 infection increased the morbidity in TBI patients by prolonging their hospital stay. One reason responsible for this might be the inability to send the admitted patient's home from hospital due to nationwide lock down impeding transport facilities. Longer hospital stay in the initial phase of pandemic can also be attributed to initial skepticism of the treating team in discharging a COVID-19 patient with head injury, as the natural course of the disease was not well known. Moreover, relatives and patients during the complete lockdown phase encountered difficulties in arranging for the transport of the patient to far flung areas. As the experience of our team grew, we were able to discharge patients earlier for care at home and by September 2020 most lockdown restrictions had also been eased, which made travel across districts/states a lot easier. This was supported by the subgroup analysis, which revealed that the longer duration of hospital stay was mainly seen in the initial part of the pandemic. The time needed for induction as well as the total operative time of TBI patients in Arm-A was statistically significantly longer than those in Arm-B. Similar trends were seen when COVID-19 positive TBI patients in Arm-A were compared with matched controls from Arm-B. But there was no such difference noted between the COVID-19 positive and COVID-19 negative patients in Arm-A. This difference can be attributed to the fact that, during the initial part of the pandemic, suspected or COVID-19 positive patients were operated by surgeons donning full PPE which decreased the dexterity and led to increased operative time. Moreover, to decrease the aerosol generation in such cases, instead of pneumatic or electrical drills, surgeons preferred using handheld burrs which also increased the duration of the surgery 24 . Adverse events and outcome of TBI patients J o u r n a l P r e -p r o o f During the hospital stay, patients in Arm-A had significantly higher chances of developing fever and pneumonia than those in Arm-B (50% versus 26.3%and 27.1% versus 1.7%, respectively). Also, incidence of fever and pneumonia was significantly more in COVID-19 positive TBI patients in Arm-A when compared with matched controls in Arm-B and when compared with COVID-19 negative patients in Arm-A. Fig. 4 shows the incidence of adverse events among TBI patients in Arm-A compared with Arm-B. This increased risk of fever/ pneumonia in Arm-A could be due to fewer residents than usual left to take care of non-COVID-19 patients, as 30-50% residents were posted into COVID-19 designated areas. Moreover, sterility during surgery or post-operative period is compromised when one is working after donning PPE. The increased chances of pneumonia in Arm-A might be related to the increased duration for which patients required ventilation in the postoperative period. Also, the COVID-19 positive TBI patients had a higher incidence of fever and pneumonia than COVID-19 negative patients in Arm-A which can be explained due to cytokine storms in COVID-19 positive patients. The outcome of TBI patients in Arm-A did not differ significantly when compared with matched controls from Arm-B (Fig. 5) . The GOS-E and GCS at discharge of TBI patients in Arm-A when compared with Arm-B was similar (p -0.557 and p -0.095, respectively). Also, both Arm-A and Arm-B had similar death rates (18.6% vs 14.4% respectively, p -0.423). Mortality rate, on the other hand, was similar in both the COVID-19 positive and COVID-19 negative patients in Arm-A ( 27.6% versus 15.7%, p -0.299). Also, the TBI patients in the early pandemic phase didn't have mortality significantly higher than those in the late pandemic phase (20.9% versus 15.7%, p -0.096). The factors found to have significant effect on outcome (GOS-E), on univariate analysis, were longer hospitalization, midline shift > 5mm, effaced sulci and gyri on NCCT head, larger size of hematoma (40 ml), severe TBI (GCS<=8), fever, pneumonia, meningitis, VAP during hospital stay. On multivariate analysis, severe TBI and meningitis during hospital stay were found to be statistically significant factors associated with poor outcome at discharge. Thus, despite significant J o u r n a l P r e -p r o o f differences between Arm-A and their matched controls from Arm-B in length of hospital stay, duration of ORs, incidence of fever and pneumonia; they fail to predict poor outcome in TBI patients. Also, the COVID-19 positivity status didn't predict an unfavorable outcome in TBI patients (OR 0.454, . All this suggests that the outcome of patients managed for emergency neurosurgical pathologies during the COVID-19 pandemic were the same as those managed before the COVID-19 pandemic 25 . This is a retrospective study with limited TBI patients being matched with their controls. A much larger study is needed to evaluate the effect of COVID-19 on the outcome of TBI patients. Also, with the availability of vaccines now during the second wave in our country, the role of COVID-19 in increasing the morbidity among TBI patients remains controversial. Further study is needed to evaluate such outcomes. COVID-19 imposed several challenges to healthcare workers in managing TBI patients during the pandemic. Guidelines for management of TBI patients during the COVID-19 pandemic were formulated for our department. The outcome of the patients managed for TBI during the COVID-19 pandemic was similar to matched patients with TBI managed at our center before the onset of COVID-19 pandemic despite the logistic problems leading to increased time required to shift patients from ED to operating room, increased duration of surgical intervention and length of hospital stay. This suggests that the guidelines followed during the COVID-19 pandemic were effective in dealing with TBI patients. This model can serve as a guide for any future pandemic wave for effective management of TBI patients without compromising their outcome. Trial. JAMA. 2021;325 (14) J o u r n a l P r e -p r o o f Formulation of HICC guidelines for use of PPEs in different hospital settings. Closure of physical OPD and use of telemedicine for patient follow-up. J o u r n a l P r e -p r o o f Serum biomarkers as predictors of long-term outcome in severe traumatic brain injury: analysis from a randomized placebo-controlled Phase II clinical trial Preparedness and guidelines for neurosurgery in the COVID-19 era: Indian perspective from a tertiary care referral hospital Preliminary Recommendations for Surgical Practice of Neurosurgery Department in the Central Epidemic Area of 2019 Coronavirus Infection Adapting Neurosurgery Practice During the COVID-19 Pandemic in the Indian Subcontinent How I do it-the posterior question mark incision for decompressive hemicraniectomy The Coronavirus Disease Global Pandemic: A Neurosurgical Treatment Algorithm The management of emergency spinal surgery during the COVID-19 pandemic in Italy: a preliminary report Letter: COVID-19 Pandemic: Safety Precautions for Stereotactic Radiosurgery Coronavirus Disease 2019 (COVID-19) and Neurosurgery: Literature and Neurosurgical Societies Recommendations Update COVID-19) Pandemic The Impact of COVID-19 on The Effects of Lockdown During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on Neurotrauma-Related Hospital Admissions. World Neurosurg COVID-19 contacts in India Therapeutic Potential for Tetracyclines in the Treatment of COVID-19 Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease Treatment for COVID-19: An overview Effect of Ivermectin on Time to RTA -Road traffic accident FFH-Fall from height temporo-parietal Decompressive craniectomy CM-Conservative management of TBI. SDH-Subdural Hematoma EDH-Extradural Hematoma O-Tocilizumab 8mg/kg (upto 800mg) single intravenous injection, repeat dose after 12 hours if no Credit Author statement MBBS -Data retrieval, Analysis, Writing manuscript, Approved final manuscript MCh -Analysis, Software, Writing manuscript, Approved final manuscript Dr Amol Raheja, MCh -Writing manuscript Dr Vivek Tandon, MCh -Conceptualization, Writing manuscript, Approved final manuscript MCh -Writing manuscript, Approved final manuscript MCh-Writing manuscript, Approved final manuscript Dr Gyaninder Pal Singh, MCh -Writing manuscript, Approved final manuscrip MCh -Writing manuscript, Approved final manuscript MCh -Writing manuscript, Approved final manuscript MCh -Writing manuscript, Approved final manuscript MCh -Writing manuscript, Approved final manuscript MCh -Writing manuscript, Approved final manuscript MCh -Writing manuscript, Approved final manuscript MCh -Writing manuscript, Approved final manuscript MCh -Writing manuscript, Approved final manuscript