Category Archives: Collaborative

Apple and Orange

Guest blog: Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic: how to compare apples and oranges?

Authors: Kenneth A McLean, Sivesh K Kamarajah, James C Glasbey

Early in the pandemic, it was recognised that patients had a higher rate of death associated with pulmonary complications if they become infected with SARS-CoV-2 in the perioperative period 1. However, the key question is why? Was this solely down to SARS-CoV-2 infections, was this due to differences in who was prioritised for surgery, or due to some other reason? These are difficult questions to answer, especially without comparable data from the pre-pandemic period. 

To address this, our paper published in the BJS pools together two large-scale, prospective and multi-specialty international cohorts 2: one from the pre-pandemic period from the STARSurg Collaborative 3 and another from during the pandemic from the COVIDSurg collaborative 4. Since these projects both included elective abdominal cancer surgery patients, and collected similar data on them and their postoperative outcomes, we were able to make a fair comparison between these cohorts. 

Overall, there was only a minority of patients with a perioperative SARS-COV-2 infection (4.3%), which is reassuring that most patientsundergoing surgery during this period were safeguarded. Interestingly, when postoperative outcomes were compared between the periods, the pulmonary complication rate observed was relatively similar (7.1% [before] vs 6.3% [during], p=0.158) but the 30-day mortality was much higher (0.7% [before] versus 2.0% [during], p<0.001). This was perhaps due to more “severe” pulmonary complications during the pandemic, e.g. a higher proportion of patients with acute respiratory distress syndrome. 

Overall, we estimated the number of deaths related to pulmonary complications (the “population attributable fraction”) increased from 37.0% (95% CI: 14.6% – 64.1%) pre-pandemic to 66.0% (95% CI: 48.6% – 79.3%) during the pandemic. This is (perhaps unsurprisingly) difficult to tease out the exact role of SARS-COV-2 infection in this – not least because SARS-COV-2 infections didn’t exist in the pre-pandemic group. We also found some major differences in patient selection and surgical practice during the pandemic. For example, while patients operated during the pandemic tended to have an overall lower baseline risk of pulmonary complications, they still had higher rate of open operations (this may be at least in part due to uncertainty at the time whether or not laparoscopic surgery was high-risk for COVID-19 transmission 5). To allow us to account for these differences in the cohorts, we used a technique called “mediation analysis”, which allows us to estimate exactly how much SARS-COV-2 infection contributed to (“mediated”) 30-day postoperative mortality during the pandemic.  

Figure 1: Multivariable natural effects model of postoperative death associated with time period, mediated by SARS-COV-2 infection.

We found that even after adjustment, there was still an almost 3-times higher likelihood of death when being operated on during the pandemic, compared to pre-pandemic (OR: 2.72, 95% CI: 1.58 to 4.67, p<0.001). However, we estimated that over half of excess deaths (54.8%) during the pandemic were explained by the presence of a SARS-CoV-2 infection. If in a parallel universe these patients were operated on pre-pandemic (e.g. with no risk of SARS-CoV-2 infection) there would still have likely been a higher rate of death than expected (perhaps due to a collateral impact on other hospital services from the pandemic that reduced capacity to rescue). However, overall, there would have been no significant difference in postoperative mortality during the pandemic (OR:1.57, 95% CI: 0.91 to 2.73, p=0.108), compared to pre-pandemic. 

In the first pandemic wave, despite attempts by care providers to continue safe elective surgery by operating on lower-risk patients, a significantly higher risk-adjusted mortality was observed. Whilst over 50% of excess deaths were explained by SARS-CoV-2 infection, the remainder may indicate a collateral impact on other hospital services that reduced capacity to rescue. The COVID-19 pandemic isn’t over yet, and upscaling elective surgery safely to meet the backlog is one of the major challenges facing health systems going forward. This study highlights the ongoing need for governments to ensure hospitals have Covid secure pathways 6 and to take appropriate and timely measures to ensure hospitals services aren’t overwhelmed. Several million patients have had their cancer surgeries delayed or cancelled 7, and there are serious concerns that despite best efforts to prioritise care this may lead to reductions in cancer survival in the long-term 8. It is likely to be several years until universal vaccination is available, and so until then strategies to mitigate risk of SARS-COV-2 infection must be implemented to continue surgery safely. 

References:

1.         Cai M, Wang G, Zhang L, Gao J, Xia Z, Zhang P, et al. Performing abdominal surgery during the COVID-19 epidemic in Wuhan, China: a single-centred, retrospective, observational study. Br J Surg. 2020;107(7):e183-e5.

2.         STARSurg Collaborative and COVIDSurg Collaborative. Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic: a comparative analysis of two prospective international cohort studies. BJS. 2021;[in press].

3.         STARSurg Collaborative. REspiratory COmplications after abdomiNal surgery (RECON): study protocol for a multi-centre, observational, prospective, international audit of postoperative pulmonary complications after major abdominal surgery. British Journal of Anaesthesia. 2020;124(1):e13-e6.

4.         COVIDSurg Collaborative. Outcomes of Elective Cancer Surgery During the COVID-19 Pandemic Crisis. 2020 [updated 12/05/20. Available from: https://clinicaltrials.gov/ct2/show/NCT04384926.

5.         Spinelli A, Pellino G. COVID-19 pandemic: perspectives on an unfolding crisis. British Journal of Surgery. 2020;107(7):785-7.

6.         Glasbey JC, Nepogodiev D, Simoes JFF, Omar O, Li E, Venn ML, et al. Elective Cancer Surgery in COVID-19–Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study. Journal of Clinical Oncology. 2020:JCO.20.01933.

7.         COVIDSurg Collaborative. Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans. The British journal of surgery. 2020;107(11):1440-9.

8.         COVIDSurg Collaborative. Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study. The Lancet Oncology. 2021.

Guest blog: Emergency surgery in patients with COVID-19

J Osorio, Z Madrazo, S Videla, B Sainz, A Rodríguez-González, A Campos, M Santamaría, A Pelegrina, C González-Serrano, A Aldeano, A Sarriugarte, C J Gómez-Díaz, D Ruiz-Luna, A García-Ruiz-de-Gordejuela, C Gómez-Gavara, M Gil-Barrionuevo, M Vila, A Clavell, B Campillo, L Millán, C Olona, S Sánchez-Cordero, R Medrano, C A López-Arévalo, N Pérez-Romero, E Artigau, M Calle, V Echenagusia, A Otero, C Tebe, N Pallares, S Biondo, COVID-CIR Collaborative Group Members of the COVID-CIR Collaborative Group

Emergency surgeons may find ourselves attending patients who are potential candidates for emergency surgery and have a COVID-19 infection, with or without evident symptoms. What should we do with these patients? 

The purely descriptive studies published to date show that these patients have a much higher than usual postoperative mortality. Considering these results, avoidance or postponement of surgery has been advised in COVID-positive patients.

However, postponing an emergency surgery may also have its risks. In each individual case, the risk of operating must be weighed against the risk of a non-surgical treatment. Therefore, it is very important to fully understand how and to what extent COVID-19 infection increases postoperative mortality.

Or in other words, is the high mortality observed in COVID-positive patients undergoing surgery entirely due to COVID-19 infection?

If we look closely at these descriptive non comparative studies, most of the COVID-positive patients were older than usual, with many underlying pathologies, and in poor general condition at the time of surgery. Could these factors, rather than the COVID-19 infection itself, explain their bad postoperative outcomes?

Additionally: During the lockdown, patients might have had fear or difficulty of going to the hospital and might therefore be diagnosed in a more advanced stage of their surgical pathologies. Moreover, the collapse of the pandemic could also cause hospitals to have difficulties in rescuing patients with postoperative complications.

If we can measure the true impact of these 3 factors involved (the patient’s context, the lockdown effect and the effect of hospital collapse) we will be able to assess how COVID-19 infection increases the mortality of patients undergoing emergency surgery. And that will allow us to make decisions based on evidence about whether, in each specific case, it is more reasonable to operate or to try not to do so.

The COVIDCIR project was born with the objective of answering that question. From the Bellvitge University Hospital, in Barcelona, we led a registry with 25 participating Spanish hospitals including all emergency general and gastrointestinal surgeries performed during the first wave of the pandemic (from March to June 2020) and during the same period of 2019 . More than 5,000 patients were included.

To assess the impact of COVID infection, we compared COVID-positive patients with COVID-negative patients operated on during the pandemic. This comparison was made using a statistical method called propensity-score matching, which consists of matching COVID-positive patients with COVID-negative controls of similar age, underlying pathologies and general condition at the time of surgery, thus achieving two comparable groups.

We observed that the mortality of these two matched comparable groups was not statistically different. Or, put another way, that the high mortality observed in COVID-infected patients undergoing surgery is more due to their age, underlying pathology and preoperative condition than to a hypothetical COVID risk-multiplier effect.

Thus, the fact that a patient is COVID-positive should not be seen as an absolute impediment to perform an emergency surgery. In each individual patient, the assessment of the risk of performing or postponing surgery should be based, as has always been done, on her or his individual anesthetic risk and its state at the time of diagnosis.

Second, to understand the effect of lockdown, to see if patients were diagnosed too late due to fear or difficulty in accessing, we compared surgical pathologies of COVID-negative patients operated on during the pandemic with those operated during the previous year. We saw that in the pandemic, patients did not present with more advanced peritonitis and that the inflammatory parameters of their laboratory tests were not higher. Thus, the increased mortality observed during the pandemic cannot be attributed to the effect of lockdown.

And finally, to understand the consequences of hospital collapse, we assessed what is called Failure to Rescue of patients: that is, what percentage of patients who present postoperative complications could not be rescued and died as a consequence of the complication. We compared Failure-to-Rescue of COVID-negative patients operated during the pandemic with those operated before the pandemic. Also on this occasion we carried out the propensity-score matching comparison, matching patients from both groups from the same hospital and of similar age, underlying pathologies and severity of surgical pathology.

We found that COVID-negative patients operated on during the COVID-19-pandemic had the same risk of postoperative complications, but a greater Failure-to-Rescue than before. This fact was evident in the 25 participating hospitals and is probably explained by the hospital collapse in the pandemic context.