key: cord-0883970-1fo4srbd
authors: Patralekh, Mohit Kumar; Jain, Vijay Kumar; Iyengar, Karthikeyan P.; Upadhyaya, Gaurav Kumar; Vaishya, Raju
title: Mortality escalates in patients of proximal femoral fractures with COVID-19: A systematic review and meta-analysis of 35 studies on 4225 patients
date: 2021-04-20
journal: J Clin Orthop Trauma
DOI: 10.1016/j.jcot.2021.03.023
sha: a829334d29727aa5b80fc4c67ff1c23c4dcfaa9f
doc_id: 883970
cord_uid: 1fo4srbd

BACKGROUND: Concerns have been raised about the escalated mortality in patients of proximal femoral fractures (PPFs) with COVID-19. A meta-analysis to evaluate mortality in patients with PPFs managed during the current COVID-19 pandemic was conducted. METHODS: A systematic review and meta-analysis of all published studies were conducted with a search on PubMed, Scopus, Web of Science, and Cochrane Library databases using appropriate keywords from January 01, 2020 to January 29, 2021. RESULTS: 35 relevant studies reporting 3979 patients with hip fracture in the current ongoing pandemic, out of which 692 patients were COVID -19 positive. Twenty studies reported mortality and other relevant statistics on hip fracture patients with and without COVID 19 (4123 hip fracture patients in the year 2020–21, out of which 560 had or were suspected of having COVID -19). A meta-analysis of mortality statistics in patients with and without COVID revealed increased odds of mortality among COVID patients [odds ratio (OR) 6.31, 95% confidence interval (CI) [5.09, 7.83] and meta-analysis on the subgroup of surgically treated patients also showed markedly increased mortality risk among those with COVID-19 (OR) 5.99, 95% CI [3.88,9.24]. CONCLUSION: The mortality risk is markedly increased in hip fracture with concomitant COVID -19 compared to those without it. This increased risk persisted in those managed surgically. It could be due to the inflammation induced by the fracture or surgery for fracture fixation, further exacerbating inflammation, leading to cytokine storm. It is imperative that such patients are informed regarding increased mortality risk during the consent and shared decision-making process.

The novel Coronavirus SARS-CoV-2 outbreak started in Wuhan, China, in December 2019, spread 32 globally and has been declared a pandemic by the World Health Organisation on 11 th March 2020 [1] . 33

Since the novel Coronavirus SARS-CoV-2 outbreak is highly contagious, managing acute trauma and 34 orthopedics had to be rationalized and re-organized to avoid viral transmission and provide a continuity 35 of care [2] . Management of patients with acute orthopedic trauma during the COVID-19 pandemic has 36 been guided by national governments' recommendations and specialist orthopedic associations [3, 4, 5] . 37

Fragility hip fractures in the elderly are obligatory injuries that require prompt surgical management to 38 allow immediate postoperative full weight-bearing mobilization supported by a multi-disciplinary team 39 to expedite rehabilitation and early supported discharge [1] . The management of proximal femoral 40 fractures (PFF) is still a surgical priority now, with an additional risk factor of . 41

Traditionally the 30-day mortality rate in patients with PFF has been reported to be 5%-8% [1] . 42 However, early limited evidence published so far suggests poor outcomes with high postoperative 43 mortality in patients with a hip fracture and concomitant COVID-19 infection (available studies 44 indicate a mortality rate greater than 30%) . We have undertaken a systematic review and 45 metanalysis to evaluate the impact of COVID-19 on patients with PFF and assessed associated 46 mortality. 47

Mortality risk was markedly higher among proven COVID-19 patients/suspected patients with hip 166 fractures than those without it, as depicted in the metanalysis of 19 studies. (Mantel Haenszel Odds 167 Ratio (MH-OR) 6.31, 95% confidence interval (CI) [5.09, 7 .83]; Z=16.75, p<0.0001, I 2 =26% so Fixed 168 effects model was used) (Figure 2A and 2B) .Overall, out of 560 covid positive or suspected hip fracture 169 cases, 205(36.61%) had expired, in contrast to only 306(8.6%) deaths among non covid cases. 170 J o u r n a l P r e -p r o o f

The separate sensitivity analysis considering test positive versus COVID-19 test-negative patients, as 171 reported in the parent studies, also revealed significantly higher among those who test positive for 172 COVID -19 patients with hip fractures than those without it. 95% CI [3.88, 9.24] ; 173 Z=11.89 ,p<0.001, I 2 =18% so Fixed effects model was used). ( Figure 3A Several studies have evaluated the outcome of hip fracture surgery in COVID-19 patients . It 183 appears equivocal that COVID-19 had an overwhelming effect on managing hip fracture patients 184 during the pandemic, with reportedly increased morbidity and mortality in these patients ' cohorts. 185 However, surgical practice in treating principles has remained the same [16] . 186

Our metanalysis shows that PFF patients with COVID-19 have higher mortality rates than those 187 without COVID-19. This effect of COVID -19 infection leading to elevated mortality rates persists in 188 the PFF patients treated surgically. A biologically plausible explanation for this effect could be the 189 fracture inflammation or surgery for fracture fixation, further exacerbating inflammation in concomitant infection due to their low functional reserves and weaker immunity [8, 9] . A combination 203 of comorbidities and elderly age could make these patients who sustain PFFs more vulnerable to 204 respiratory illness due to their limited pre-injury ambulatory status [24] . 205 PFF is an obligatory injury that requires prompt surgical management to allow early mobilization, 206 reduce pain, and prevent problems associated with recumbency [9, 14] . According to the prioritization 207 list of surgical procedures, PFF belongs to the group IA requiring surgery to be undertaken 24 hours or 208 so from the presentation. Hence appropriate pre-operative medical optimization and an emphasis for 209 surgical stabilization to be undertaken throughout the COVID-19 situation has been a clinical goal [4] . 210

The usual recommendation has been that hip fracture patients should be operated on as soon as they are 211 medically fit. More than 48 hours after admission, any surgical delays may escalate the odds of 30-day 212 all-cause mortality [9] . 213 214 Early and limited available evidence suggests poor outcomes with high postoperative mortality of more 215 than 20%-30% in patients contracting COVID-19 in the perioperative phase [5, 6, 74] The orthopedic community's challenge is finding a balance of providing an effective treatment option 252 for PFF and achieving the best eventual outcome for these patients to reduce mortality and be mindful 253 of associated risk factors and comorbidities. 254

These studies were done in different geographical populations. Consequently, availability, quality of 256 medical care, and surgical facilities may vary. These factors may reflect on clinical outcomes. Only a 257 few studies focussed on the PFF exclusively, whereas others had included all types of fractures. All 258 relevant variables were not reported uniformly in the studies. There is a lack of uniformity in the patient 259 population, which may affect the risk of mortality and morbidity. Follow up period of patients was also 260 variable, and relatively short-term outcomes have been reported. Extended outcomes have not been 261 described. In-patient and 30-day mortality was explicitly mentioned in a few studies only. 262

Another limitation of the study has been the nature of studies that have been reported and available for 263 analysis. Any study based on the recruitment of retrospective cohort studies is prone to various bias and 264 confounding factors, particularly of publication and detection bias. However, we have utilized funnel 265 plots to explore the potential of publication bias. To mitigate detection bias, evaluation of relevant 266 recent literature and application of PRISMA reporting principles of a systematic review have been 267 incorporated. 268

This systematic review and meta-analysis confirm that hip fracture patients with COVID-19 have 270 significantly higher mortality rates than non-COVID patients. The 30-day mortality rates are also 271 higher in these groups of patients. The enhanced effect of COVID-19 infection leading to elevated 272 mortality rates persists in hip fracture patients treated surgically. The likely contributory factors for 273 increased mortality are inflammation caused by the fracture and the surgery (leading to Cytokine-274 storm), advanced age, male sex, and perhaps early surgical intervention. Informed consent must include 275 a disclosure of the increased risk of mortality after the surgery of PFF and must be explained clearly to 276 the patient and their relatives. The treating surgical team should carefully do a due risk-benefit analysis. 

CAD-Coronary artery disease; CCS-Surgery with Cannulated cancellous screws; COPD-Chronic obstructive pulmonary disease; C+ve -Coronavirus disease 2019 positive; C susp-Coronavirus disease

CKD-Chronic kidney disease; CT-Computed Tomography scan; CVA-Cerebrovascular accident; DHS-Dynamic hip screw surgery

FN-Femoral neck fracture

GT-Greater trochanter fracture

ILN-Interlocking nail surgery; IT-Intertrochanteric fracture

ORIF-Open reduction and internal fixation; PVD-Peripheral vascular disease

RT PCR-Reverse Transcriptase Polymerase Chain Reaction

Total fractures: Neck femur/intracapsular-Pertrochanteric/extracapsular

J o u r n a l P r e -p r o o f