key: cord-0764062-qxwwtipu
authors: Zheng, Hua; Hébert, Harry L.; Chatziperi, Athanasia; Meng, Weihua; Smith, Blair H.; Yan, Jing; Zhou, Zhiqiang; Zhang, Xianwei; Luo, Ailin; Wang, Liuming; Zhu, Wentao; Hu, Junbo; Colvin, Lesley A.
title: Perioperative management of patients with suspected or confirmed COVID-19: review and recommendations for perioperative management from a retrospective cohort study
date: 2020-09-04
journal: Br J Anaesth
DOI: 10.1016/j.bja.2020.08.049
sha: daa7f80ee78585f3d8f6c649e71fa4abf50177b7
doc_id: 764062
cord_uid: qxwwtipu

BACKGROUND: Current guidelines for perioperative management of COVID-19 are mainly based on extrapolated evidence or expert opinion. We aimed to systematically investigate how COVID-19 affects perioperative management and clinical outcomes, to develop evidence-based guidelines. METHODS: First, we conducted a rapid literature review in Embase, Medline, PubMed, Scopus, and Web of Science (1(st) January to 1(st) July 2020), using a predefined protocol. Secondly, we performed a retrospective cohort analysis of 166 women undergoing Caesarean section at Tongji Hospital, Wuhan during the COVID-19 pandemic. Demographic, imaging, laboratory, and clinical data were obtained from electronic medical records. RESULTS: The review identified 26 studies, mainly case reports/series. One large cohort reported greater mortality in elective surgery patients diagnosed after, rather than before surgery. Higher 30-day mortality was associated with emergency surgery, major surgery, poorer preoperative condition and surgery for malignancy. Regional anaesthesia was favoured in most studies and personal protective equipment (PPE) was generally used by healthcare workers (HCW), but its use was poorly described for patients. In the retrospective cohort study, duration of surgery, oxygen therapy and hospital stay were longer in suspected or confirmed patients than negative patients, but there were no differences in neonatal outcomes. None of the 262 participating HCWs was infected with SARS-CoV-2 when using level 3 PPE perioperatively. CONCLUSIONS: When COVID-19 is suspected, testing should be considered before non-urgent surgery. Until further evidence is available, HCWs should use level 3 PPE perioperatively for suspected or confirmed patients, but research is needed on its timing and specifications. Further research must examine longer-term outcomes. REGISTRATION: The rapid review was registered in PROSPERO (ID: CRD42020182891).

protective equipment; SARS-CoV-2 testing 1 2

The impact of COVID-19 on the perioperative management and clinical outcomes 4

were systematically investigated to develop evidence-based guidelines for 5 management. 6 A rapid review of 26 studies, mainly case reports/series, found greater mortality in 7 elective surgery patients diagnosed after, rather than before surgery. 8

Higher 30-day mortality was associated with emergency surgery, major surgery, 9

poorer preoperative condition and surgery for malignancy. 10

A retrospective cohort study found that duration of surgery, oxygen therapy and 11

hospital stay were longer in suspected or confirmed patients with COVID-19 than in 12 negative patients, with no differences in neonatal outcomes from Caesarean 13 delivery. 14 None of the participating HCWs was infected with SARS-CoV-2 when using level 3 15 PPE perioperatively. 16 17 18 19 J o u r n a l P r e -p r o o f Disagreements were resolved via discussion between the two reviewers. Recommendations for the perioperative management of patients with COVID- 19 2 were developed from the synthesised evidence, and tables were constructed to aid 3 the presentation of the extracted data and quality assessment of each article. 4 5

Study design and data sources and ethics 7

This single-centre, retrospective study was approved by the Institutional Review 8

Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and 9

Technology (TJ-IRB20200421). The requirement for informed consent from 10 participants was waived under the regulations of the Institutional Review Board. 11

Data, including demographic, clinical, imaging, laboratory, perioperative 12 management, and maternal and fetal outcomes, were extracted from the electronic 13 database of medical records at Tongji Hospital, and anonymised for analyses. 14 Data from all parturients who underwent Caesarean section (including emergency 15 surgery) during the COVID-19 pandemic in Wuhan were included. In order to ensure 16 completeness of reported data, we included all patients who had undergone 17

Caesarean section in the defined time period; some of these data have been 18 reported previously by other groups 13, 14 . 19 COVID-19 case definitions were based on the National Health Commission of China's 20 diagnostic criteria (7 th edition) (Box 1) 15 Before entering the operating room, triage was performed by obstetricians and 3

anaesthetists, including a medical history review, brief physical examination, and 4 review of blood test results, CT, and tests for SARS-CoV-2 nucleic acid or antibodies. 5

Because individuals might be infected with SARS-CoV-2 but be asymptomatic, all 6 patients were placed in an isolation holding area and transferred to a dedicated 7 negative pressure operating room with an anteroom (buffer area). Patients wore 8 surgical or N95 masks throughout the process. After the patient entered the 9 operating room, continuous electrocardiography, regular non-invasive blood pressure, 10 and peripheral pulse oximetry were monitored. Spinal anaesthesia or combined 11 spinal-epidural anaesthesia was the primary technique. General anaesthesia with 12 tracheal intubation was an option under certain circumstances such as 13 contraindications of spinal anaesthesia, maternal or fetal emergencies, or failed 14 spinal anaesthesia. During tracheal intubation, surgeons and nurses remained in the 15 operating room to ensure that surgery started as soon as possible after induction. 16

The neonatal team was notified before delivery in order to attend and make any 17 necessary preparations. After delivery, newborns were cleaned immediately to 18 remove blood clots, meconium and amniotic fluid, and were then placed under a 19 radiant warmer in a cordoned-off area in the operating room. Apgar scores of 20 newborns were assessed at 1 and 5 min. For patients with suspected or confirmed 21 COVID-19, their newborns were transferred to a neonatology isolation room shortly 22 after delivery. SARS-CoV-2 nucleic acid tests were then carried out as soon as 23 possible in all newborns. Maternal contact was not allowed. 24

One day after surgery, full blood count and coagulation tests were performed in 25 parturients. If COVID-19 was suspected or confirmed, chest CT, SARS-CoV-2 nucleic 26 acid or antibodies were tested again. Body temperature or any other symptoms 27 associated with COVID-19 were recorded daily by nurses throughout the hospital stay. 28

According to parturients' clinical condition, supplemental oxygen was delivered via 29 nasal cannula or mask to maintain an SpO2 of 95% or above. Other methods of 1 non-invasive or invasive ventilation were considered if necessary. Diclofenac and/or 2 dezocine was given, as requested by the parturients, to relieve postoperative pain. 3 4 Perioperative protection and postoperative evaluation of healthcare workers 5 Self-protection precautions were strictly followed by all participating HCWs. Level 3 6 PPE, including N95 mask, fluid-resistant gown, goggles, face shield, disposable hair 7 cover, head covering, two layers of gloves, and fluid-resistant shoe covers, was used 8 by all HCWs involved. PPE was donned before entering the operating room and was 9 doffed after exiting operating room in buffer area. All HCWs involved had a 24-h duty 10 shift every one to two weeks. They were required to report any COVID-19 related 11 symptoms such as fever, cough or fatigue. At the beginning of April, 2020, all HCWs 12 were required to have a SARS-CoV-2 antibody test, a test for SARS-CoV-2 nucleic acid 13 by nasopharyngeal swab, and a chest CT scan. 14 15

Suspected or confirmed cases were categorised together and compared with 17 negative cases. Maternal outcomes including duration of operation, oxygen therapy, 18 hospital stay, and fetal outcomes such as Apgar scores were compared between 19 groups. Continuous variables are presented as median (IQR). These data failed the 20 The workflow for identifying and screening articles is provided in figure 1 . The initial 4 literature searches yielded 3,227 papers. The re-run of the search yielded a further 5 107 articles. After removal of duplicates, non-English language papers and title and 6 abstract screening, 64 articles remained for full-text review. Articles identified during 7 the re-run of search terms (from 4 th May to 1 st July, 2020) that were excluded on the 8 basis of having a sample size ≤15 are shown in Supplementary Table S4 . A full list of 9 the 38 articles excluded on full-text review, with reasons, is provided in 10 Supplementary Table S5 . We therefore identified 26 articles for inclusion in this 11 review . 12

The characteristics of each included study are summarized in Table 2 . There were no 14

RCTs, and 22 of the papers were lower quality case reports or case series 16, 17, 19, 21-32, 15 34-39, 41 . The remaining 4 were observational studies, of which 2 were cohort studies 20, 16 33 , 1 was a small cross-sectional study (n=7) 18 Tables S6 and S7.  1 Due to the limited sample sizes of the included studies, the heterogeneity in 2 surgeries performed and approaches to perioperative management, and the inherent 3 lack of comparative groups in the case reports, it was not possible to conduct a 4 meta-analysis to estimate effect sizes and we could not quantitatively assess risk of 5 bias across studies. 6

Diagnosis of COVID-19 and timing of diagnosis (relative to surgical procedure) were 8 variably reported, applying a range of diagnostic criteria. Suspected COVID-19 was 9 usually based on relevant symptoms. All of the studies used RT-PCR for SARS-CoV-2 10 RNA or chest CT for diagnosis (though 1 study did not report diagnostic criteria 32 ). 11

Four studies used RT-PCR only 26, 29, 31, 35 , 2 studies used CT only 18 Three studies reported on the decontamination of the anaesthesia machine 2 following surgery 19, 24, 40 , with two of the studies reporting no HCW infection with 3 SARS-CoV-2 19 , 24 (the third study did not report HCW COVID-19 status 40 ). A further 4 study reported the discarding of disposable anaesthetic devices after single use 27 . 5

Patient outcomes reported included length of hospital stay, requirement for critical 7 care, level of respiratory support and respiratory complications, discharge status, and 8 mortality (Supplementary Table S9 ). None of the included studies reported on all 9 these outcomes. Reporting on discharge status was very limited. Twelve studies 10 reported length of stay in hospital, which ranged from 5 to 52 days [18] [19] [20] 22 , 25, 26, 28-31, 33, 11 35 . 12

In the largest cohort study (n=1,128), the median length of stay in hospital (IQR) was 13 10 days (3-27) for minor surgery and 17 days (8-29) for major surgery, reported in a 14 total of 1,083 patients 33 . This study reported an overall 30-day mortality of 23.8%, 15 with a higher rate of mortality in patients undergoing elective surgery where the 16 presence of SARS-CoV-2 virus had been confirmed postoperatively rather than 17 preoperatively (20.4% vs 9.1%). A number of patient factors were found to be 18 associated with higher 30-day mortality including male sex (odds ratio [ However, we can only make tentative recommendations on the use of PPE as it was 28 not clearly reported how long PPE was worn before, during and/or after the surgery 29 J o u r n a l P r e -p r o o f and whether any changes were made to the level of PPE worn at any stage (for 1 example following intubation/extubation of the patient). Furthermore, we cannot be 2 sure that HCW infection occurred as a result of caring for patients with COVID- 19 3 rather than other sources such as infected colleagues or in the wider community 41 . Caesarean section and were included in this study. Before surgery, 2 patients were 9

confirmed to be infected with SARS-CoV-2 and 36 patients were considered as 10 suspected cases based on the above criteria (Box 1). After surgery, 5 suspected cases 11 were confirmed and 11 suspected cases were ruled out. Finally, 7 confirmed cases 12 and 20 suspected cases of COVID-19 were identified. One case report 14 Caesarean section between 1 st January, 2020 and 23 rd January, 2020 were not 16 included in the current study. All 20 suspected cases had imaging features of 17 COVID-19. They were tested with RT-PCR only before discharge and the results were 18 negative. For analysis, we combined these suspected cases and confirmed cases as 1 19 group (n=27) and patients not (suspected to be) infected with SARS-CoV-2 as a 20 second 'negative' group (n=139). As shown in Supplementary Table 10, the BMI of 21 suspected or confirmed patients was higher than that of negative patients (P = 22 0.034). Symptoms associated with COVID-19 occurred only in suspected or confirmed 23 patients; fever was the commonest with an incidence of 44.4%, followed by cough 24 (14.8%) and diarrhoea (3.7%). 25

Laboratory findings of patients before and after Caesarean section are summarised in 26 Supplementary Table 11 . Compared with baseline pre-procedural values, increased 27 leukocyte and neutrophil counts were observed after surgery in all patients. 28

Compared with negative patients, suspected or confirmed patients had lower 29 leukocyte (P = 0.003 before surgery; P = 0.047 after surgery) and lymphocyte (P = 1 0.030 before surgery; P = 0.041 after surgery) counts during the perioperative period. 2

Baseline preprocedural C-reactive protein levels in confirmed or suspected patients 3 were higher than negative patients (P = 0.014), but were not difference from 4 postsurgical levels. In negative patients, there were significantly elevated levels of 5 CRP (P = 0.006) and D-dimer (P = 0.011) after surgery compared with baseline 6 preprocedural values. 7

Characteristics of anaesthesia and surgery 8 An overview intraoperative characteristics is shown in Supplementary Table 10. 9

Regional anaesthesia was the commonest type of anaesthesia and was performed in 10 142 (85.5%) of parturients. Duration of operation in suspected or confirmed patients 11 was longer than that in negative patients (P = 0.003). However, there were no 12 significant differences in blood loss, fluid management, or use of vasoactive drugs 13 and flurbiprofen. 14 Maternal and fetal outcomes 15

As listed in Supplementary Table 10, 48.8% of patients received diclofenac and/or 16 dezocine for postoperative pain. There was no significant difference between 17 suspected or confirmed patients and negative patients. Both the duration of oxygen 18 therapy (P < 0.001) and length of hospital stay (P < 0.001) were significantly longer in 19 suspected or confirmed patients than negative patients. No suspected or confirmed 20 patients developed severe pneumonia or received non-invasive or invasive 21 mechanical ventilation. However, a negative patient with liver cancer was intubated 22

and died due to pulmonary embolism after surgery. 23

The median Apgar scores were 8 at 1 min and 9 at 5 min. There were no apparent 24 differences between neonates in the suspected or confirmed group and the negative 25 group. In the negative group, a neonate delivered at 25 weeks gestation died 10 min 26 after birth. In the confirmed group, a neonatal COVID-19 infection with positive 27 RT-PCR assay results on pharyngeal swab was reported 36 h after birth, which had 28 been reported in a previous study 13 . However, the results of nucleic acid tests for 29 SARS-CoV-2 on placenta specimens, cord blood and mother's breast milk in this 1 mother-neonate dyad were all negative. 2

Postoperative evaluation of healthcare workers 3 A total of 262 HCWs including 71 anaesthetists, 60 obstetricians and 131 nurses 4 (circulating nurses, instrument nurses and neonatal nurses) were involved in these 5 Caesarean sections. Level 3 PPE was used by all the HCWs during the operation. 6

None of them reported COVID-19 related symptoms during the COVID-19 pandemic. 7

As of 15 th April, 2020, none of them has been infected with SARS-CoV-2 according to 8 chest CT findings, RT-PCR testing and/or SARS-CoV-2 antibody testing. 9

Our rapid literature review identified 26 studies reporting perioperative management 2 of patients with suspected or confirmed COVID-19. To our knowledge this is the most 3 comprehensive such review to date. Most studies were low-quality case 4 reports/series with low sample size, and even amongst the observational studies, 5 perioperative management was not necessarily the main focus of any quantitative 6 analysis conducted 20, 33 and was poorly reported 18 . Thus, a cohort study of Caesarean 7 sections, especially focusing on perioperative management and patients and HCW 8 outcomes, was performed to augment the included evidence base. 9

All studies included in the review used either RT-PCR or chest CT to diagnose 10 SARS-CoV-2/COVID-19. This approach appears to be supported by the fact that radiation, particularly for women undergoing Caesarean section whose fetus will also 19 be exposed 46 . This is an area that requires further investigation, but consideration 20 should be given to using both approaches in diagnosing COVID-19. 21

The timing of COVID-19 testing also needs to be considered since higher mortality Safety Foundation joint guidelines 50 . However this might be difficult for emergency 5 surgery, therefore a standardised diagnosis and treatment protocol for emergency 6 patients should be developed. This is already happening in some places and whilst 7 pre-operative screening will potentially increase the time between admission and 8 surgery, initial evidence suggests that this risk can be minimised to the point that it 9

can be balanced against the potential risk of performing surgical procedures in 10 COVID-19 patients 51 . Further research is needed to establish whether the testing 11 pathway is of more clinical benefit than not having it. In patients with suspected or 12 confirmed COVID-19, the COVID-19 status of newborns should also be taken into 13 account where relevant. Testing should be performed as soon as possible after 14 delivery to help prevent transmission to HCWs and to ensure risk to the newborn is 15 minimised, with early recognition and management of symptoms. 16

Despite being included in perioperative anaesthesiology guidelines for HCWs in both 17 the US and China 3, 50 , PPE use was poorly reported by studies in patients (9 studies) 19 suggesting that both regional and general anaesthesia can be delivered safely to We identified 12 studies reporting the separation of neonates from mothers 26 following Caesarean section 16, 19, 21, 23, 28, 30, 31, 34-36, 38, 39 . In our cohort study, newborns 27 of mothers with suspected or confirmed COVID-19 were also transferred to an 28 isolated observation ward after birth. At least in China, where 9 of those studies were 29 conducted, this represents a significant change from standard practice where 1 normally mother and child skin-to-skin contact is encouraged, with recognised 2 neurobiological benefits for mother and neonate. Although a newborn whose 3 mother was confirmed with COVID-19 tested positive 36 h after birth in our cohort 4 study, whether the case was a contact transmission or a vertical transmission 5 remains to be confirmed. Since the remaining studies did not accurately report level 6 of mother and child contact, it is not possible to determine whether separation 7 decreases the risk of SARS-CoV-2 infection. Emerging data suggest that allowing 8 neonates to room in with their mothers and breastfeed confers low risk of perinatal 9 and vertical transmission when a face mask is worn and proper hygiene is 10 observed 58 . Because of these clinical implications and the potential impact on 11 maternal-neonate interaction, this area requires urgent investigation. 12 A large cohort study identified patient and surgical factors associated with 30-day 13 mortality 33 . This multicentre study is easily the largest study of postoperative 14 outcomes in patients with COVID-19 and because of the size and quality of the 15 analysis, it is the only study from which we can make strong conclusions 33 . 16 Consequently, future studies should consider longer-term reporting of health 17

Previous studies found low mortality rates (1%) and requirement for respiratory 19 support (10%) amongst pregnant women with COVID-19, as well as low neonatal 20 transmission (5%), which our study supported 59, 60 . However, the duration of 21 operation, oxygen therapy and length of hospital stay were significantly longer in 22 suspected or confirmed patients than negative patients. An optimal approach to 23 perioperative management in COVID-19 patients including appropriate use of 24 anaesthetics and analgesics needs to be determined in future studies. The rapid nature of this review means that more recently published articles may have 22 been missed, though we mitigated this risk by conducting a further (targeted) 23 literature search prior to submission. Excluding those not in English is pertinent given 24 the global status of the COVID-19 pandemic. We also had to exclude 2 studies from 25

Tongji Hospital in Wuhan as some of the participants were also included in the cohort 26 study for this paper 13, 14 . J o u r n a l P r e -p r o o f

A Novel Coronavirus from Patients with Pneumonia in China

World Health Organization. Coronavirus disease (COVID-19)

Perioperative Management of Patients Infected with the Novel Coronavirus: Recommendation from the Joint Task Force of the Chinese Society of Anesthesiology and the Chinese Association of Anesthesiologists

A systematic review

Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study

A Case Report of Neonatal 2019 Coronavirus Disease in China

English version translated by the Chinese Society of Cardiology

Severe COVID-19 during Pregnancy and Possible Vertical Transmission

Treatment of Proximal Femoral Fragility Fractures in Patients with COVID-19 During the SARS-CoV-2 Outbreak in Northern Italy

Management of Spine Trauma in COVID-19 Pandemic: A Preliminary Report

Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients

Factors Associated With Surgical Mortality and Complications Among Patients With and Without Coronavirus Disease 2019 (COVID-19) in Italy

Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn

Anesthesia and protection in an emergency cesarean section for pregnant woman infected with a novel coronavirus: case report and literature review

Vaginal delivery in SARS-CoV-2 infected pregnant women in Northern Italy: a retrospective analysis

Box 1 -The National Health Commission of China's diagnostic criteria for suspected cases of COVID-19

Epidemiological history 1. History of residence or travel in Wuhan and its surrounding areas

History of contact with SARS-CoV-2 infected patients (positive results of nucleic acid test) within 2 weeks prior to the onset of the disease

History of contact with patients with fever and/or respiratory symptoms who are from Wuhan and its surrounding areas

Cluster of infections: 2 or more cases with fever and/or respiratory symptoms occurred in a small area such as home, office, and school class within 2 weeks prior to the onset of the disease

Clinical manifestations 1. Fever and/or respiratory symptoms

Imaging features of COVID-19: multiple patchy shadows and interstitial changes in the early phase, and then multiple ground-glass opacities, infiltration shadows or even consolidation in advanced-phase