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Performance of prognostic scores in prediction of 30-day postoperative mortality in COVID-19 patients after emergency surgery: A retrospective cohort study ST Karna1, R Gouroumourty2, Z Ahmad1, S Trivedi1, P Thaware1, P Singh11 Department of Anaesthesiology and Critical Care, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India 2 Department of Community and Family Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.jpgm_1197_21
Keywords: COVID-19, emergency surgery, postoperative morbidity, prognostic risk indices
Emergency surgery is associated with higher morbidity or mortality, which may further be exacerbated by coronavirus disease 2019 (COVID-19).[1–3] In surgical patients, the American Society of Anesthesiologists physical status classification (ASA-PS), Physiologic and Operative Severity Score for numeration of Mortality and Morbidity (POSSUM) and its modification, Portsmouth POSSUM (P-POSSUM), are used for risk stratification.[4–8] In critically ill patients, Sequential Organ Failure Assessment (SOFA) is routinely used whereas the Quick SOFA (qSOFA) score is used to identify sepsis in non-ICU settings.[9–10] There is paucity of literature to suggest which risk assessment score is appropriate in COVID-19 patients undergoing emergency surgery. To address this research gap, this study was conducted with the objective to study the 30-day mortality after emergency surgery in COVID-19 patients and assess the performance of these routinely used prognostic risk indices in prediction of postoperative mortality.
Study design and setting: This retrospective, observational, cohort study was conducted in a tertiary care institute, in Central India, which serves as a referral centre for COVID-19 cases. Study population: Patients above 18 years age of either gender with confirmed COVID-19, who underwent emergency surgery from 1 May 2020 to 31 October 2021 in our institute were included. We defined a positive COVID-19 laboratory test as positive via reverse transcription-polymerase chain reaction (RTPCR) test within seven weeks prior to or within one week after emergency surgery. We excluded patients with a negative COVID-19 test, pediatric patients and minor surgical procedures like re-suturing, lumbar puncture, and tracheostomies. Ethical issues: Data for this study was retrieved from another ongoing study which had received local institutional human ethics committee approval (IHEC LOP/IM03075). All patients who participated in this other study, gave their informed consent for the use of their anonymized data for scientific purposes. Outcomes: The primary outcome was to find the 30-day mortality rate and the discrimination and calibration of risk assessment scores like ASA-PS, SOFA, qSOFA, POSSUM and P-POSSUM in prediction of postoperative mortality in COVID-19 patients undergoing emergency surgery. Data collection: Perioperative anesthesia case file and electronic hospital records were used as sources of data. Besides anesthesiologists, the surgical team involved in care of the patient included obstetricians, neurosurgeons, ear, nose and throat surgeons, and general and orthopedic surgeons. Lung protective ventilation was used in all patients as a protocol during COVID-19 pandemic, ensuring driving pressure of <15 cm H2O with plateau pressure of <30 cmH2O. Compliance before start of surgery was recorded on anesthesia charts as ratio of tidal volume to driving pressure (plateau pressure minus positive end expiratory pressure). The study investigator collected the following preoperative data: demographic characteristics, comorbidities, SARS-CoV-2 infection status, diagnosis and indication of surgery, presence of acute respiratory distress syndrome (ARDS) with severity as per Berlin classification, type of oxygen support and need for intensive care.[11] The prognostic scores were calculated by a separate investigator, who did not participate in collection of postoperative data. The ASA-PS classification, and SOFA and qSOFA scores were calculated as per standard definitions in the immediate preoperative period.[4],[9],[10] The POSSUM and P-POSSUM scores are a combination of 12 weighted physiological (PS) and six operative (OS) variables obtained for individual patients.[6],[8] Both scores were evaluated with inputs regarding operative data from the surgical team. A dedicated investigator entered the patient data into an online calculator (MDCalc) which was used to calculate the PS, OS, predicted morbidity as per POSSUM, and predicted mortality as per POSSUM and P-POSSUM.[12] Furthermore, the PS and OS were added to yield a total score (TS). We noted the surgery, anesthetic and airway management techniques, need for ICU stay, morbidity over a 30-day post-operative period assessed by Clavien Dindo classification along with cumulative 30-day mortality.[13] The course of hospital stay was followed till hospital discharge or death. The data regarding postoperative complications was collected from the postoperative medical records of the patients with inputs from the surgical team involved in the care of the patient. All data collected into a standardized data collection tool by two dedicated study investigators was checked for internal consistency, completeness, and transcription errors by reviewing the patient's charts again before entry into an electronic database. Sample size In view of the exploratory nature of the study, convenience sampling was done with inclusion of all emergency surgical patients satisfying the inclusion and exclusion criteria during the study period. Statistical analysis Data entry was done in Microsoft Excel 2010, followed by analysis using statistical programming language R version 4.1.0.[14] Data was prepared for analysis using standard data cleaning and wrangling procedures using base R and the tidyverse, gtsummary packages. The model building, visualizations and diagnostics were run with the performance, ggplot, survival, and survminer packages in R software. Continuous data were summarized as mean (SD) and median (IQR) based on the distribution of data. Association between two categorical variables was determined using Chi-squared test and Fischer's exact as appropriate. Kruskal–Wallis rank sum test was used to determine the association between more than two categorical groups and the numerical determinants. The primary outcome of the analysis was a 30-day mortality. The 30-day time point was chosen because it has been used in previous evaluations of prognostic scores. The secondary outcome was the area under the curve (AUC) of the receiver operating curve (ROC) of the ASA grade, SOFA, qSOFA, POSSUM, and P-POSSUM scores. The univariate Cox proportional hazards regression analysis was used to assess hazard ratio for mortality from time of positive COVID-19 status to the final outcome. The ROC was plotted using the “ROCR” to assess the potential of the SOFA, POSSUM, and P-POSSUM scores in predicting mortality among COVID-19 emergency surgical patient; this was compared to their actual outcome of either survival or death within 30 postoperative days. The AUC was used to delineate quality of discrimination between values. For each point of measurement over the individual curve, Youden's index [YI = Sensitivity + Specificity -1] was used to determine the optimal cutoff. P value of < 0.05 was considered significant. Model performance of POSSUM and P-POSSUM was assessed by measuring their ability to discriminate between the non-survivors and survivors, observed over expected mortality ratios and calibration fit across various risk bands using Hosmer-Lemeshow goodness of fit model. Large χ2HL values suggest poor fit, with calibration considered to be poor if P ≤ 0.05.
In the study period, 5,042 COVID-19 patients were admitted to our institute. Sixty-seven patients, satisfying the study criteria, underwent emergency surgery under anesthesia in our institute. Baseline characteristics The mean age of patients was 46.3 ± 15.6 years. One or more comorbidities were present in 44 patients (66%). Sixty-three patients (94%) were diagnosed preoperatively while 4 patients (6%) tested positive after surgery. 54 patients (81%) presented with headache, altered sensorium, or with respiratory, digestive or cardiac symptoms with a frequency of 32 (48%), 1 (1.49%), 22 (32.8%), 12 (17.9%), 2 (3%) respectively. Bilateral peripheral opacities on chest radiograph were documented in 27 patients (40%) before surgery. Out of the 17 patients who had ARDS before surgery, 16 (94%) presented with dyspnea, with severity of ARDS ranging from mild, moderate, to severe in 9 (13%), 6 (9.0%) and 2 (3.0%) patients, respectively. Proning sessions were given in 13 patients. Before surgery, 12 patients were on low-flow oxygen, non-invasive ventilation was needed in 3 patients while 2 patients required endotracheal intubation and invasive ventilation. Intubation and ventilation before surgery was needed in an obstetric patient with severe ARDS and a neurosurgical patient with altered sensorium and moderate ARDS. Of the 17 patients who had ARDS before surgery, 16 (94%) were found to be diagnosed as COVID-19 positive before surgery. Intensive care support was required before surgery in 11 patients (16%): 4 patients were antenatal with COVID-19 ARDS (moderate in 3 and severe in 1); 4 patients had abdominal pathologies with associated sepsis, hemodynamic instability and ARDS; 1 had rhino-cerebral mucormycosis with coronary artery disease and cardiac failure; 1 had toe gangrene with moderate ARDS, septic shock, and 1 was a mechanically ventilated neurosurgical patient with intracranial bleed. Though the median duration from symptom onset to hospital admission was 7 (IQR 2–14) days, surgery was done 14.5 (IQR 5.5–21) days after symptom onset in our patients with COVID-19. Prognostic scores and predicted outcomes Only 24% of patients were ASA IIIE and ASA IVE. Quick SOFA score was positive (≥1) in 14 patients (21%). The median SOFA score value was 1 (IQR 0,2). The mean POSSUM predicted morbidity was 49.4% ± 23.9%. The mean physiological and operative scores were 22.7 ± 6.4 and 12.31 ± 2.68 scores for POSSUM, and 22.5 ± 6.6 and 12.3 ± 2.6 for P-POSSUM. The POSSUM and P-POSSUM predicted mortality in median (IQR) was 8.2% (5.2,16.6)% and 2% (1,7)%, respectively. Surgical treatment and type of anesthesia The most common emergency surgical procedure performed in COVID-19 patients was sinus surgery for rhino cerebral mucormycosis in 36 patients (54%) followed by obstetric in 20 (30%), gastrointestinal in 6 (9%), orthopedic in 3 (4.5%), and neurosurgery in 2 (3%) patients. Blood product transfusion was needed in 18 patients (27%). General anesthesia with endotracheal intubation was administered in 46 patients (69%). The mean lung compliance noted prior to start of surgery was low (33.2 ± 7 ml/cm H2O). Regional anesthesia was given in 21 patients (31%), mainly in obstetric and orthopedic surgeries. Postoperative complication Major complications (>3A Clavien-Dindo class) were observed in 22 patients in the postoperative period. Intensive care was needed after surgery in 21 patients (31.3%), including 8 (22%) ENT, 5 (83.3%) abdominal, 5 (25%) obstetric, 2 (100%) neurosurgery, and 1 (33%) orthopedic surgery. Most frequent complications were ARDS (26.9%), followed by sepsis (25.3%), septic shock (18%), acute kidney injury (AKI) (19.4%), multiorgan dysfunction syndrome (MODS) (12.6%), poor myocardial contractility (5.9%), arrhythmias (4.5%), and thrombotic complications (3%). The severity of complications as per Clavien Dindo classification are mentioned in [Table 1]. Amongst the 22 patients with major postoperative complications, only 9 survived.
ARDS after surgery was observed in 2 (100%) neuro, 5 (83.3%) abdominal, 1 (33.3%) orthopedic, 4 (25%) obstetric, and 6 (16.6%) sinus (ENT) surgeries. Mild, moderate, and severe ARDS was seen in 10, 4, and 4 patients, respectively. Postoperatively, invasive and non-invasive ventilation was needed in 15 (22%) and 1 (1.5%) patients, respectively. The critical care and duration of hospital stay in survivors ranged from 1–13 and 8–44 days, respectively. No significant difference was seen in the postoperative complications between those who tested COVID-19 positive before or after surgery (P = 0.6) Postoperative 30-day mortality The 30-day mortality rate was 19% with death in 13 patients. Mortality was highest in laparotomies (83%) followed by neurosurgical (50%), orthopedic (33.3%), sinus (rhino-cerebral mucormycosis) surgeries (13.9%) and lower segment cesarean sections (5%) [Figure 1].
Preoperative ARDS suggestive of COVID-19 was seen in 10 non-survivors (mild in 5, moderate in 4 and severe in 1). In the postoperative period, ARDS was noted in 12 non-survivors (mild, moderate, and severe in 5, 4, and 3 patients, respectively). New onset of mild and severe ARDS was noted in one patient each of mucormycosis and pancreatitis, along with increase in severity in 8 patients. Postoperative invasive ventilation was needed in 10/13 patients (77%) among non-survivors in contrast to only 5/53 (9.3%) of the survivors. The immediate cause of postoperative death was identified as septic shock with COVID-19 ARDS respiratory failure in 9 patients (69.5%), respiratory failure with COVID-19 ARDS in 2 patients (15.3%), post-COVID-19 mucormycosis with MODS in 1 patient, and septic shock with MODS in 1 patient. After surgery, moderate-severe ARDS was seen in 12/13 non-survivors (92.3%) compared to 1/54 survivors (1.8%). Amongst those administered general anesthesia, the non-survivors were observed to have a statistically significant higher driving pressure (21.4 ± 3.9 vs 18 ± 3.4 mmHg, P = 0.005) and lower compliance (29.8 ± 5.6 vs 34.4 ± 7.8, P = 0.049) as compared to survivors. No statistically significant difference was seen in the 30-day mortality in those who tested COVID-19 positive before or after surgery (P > 0.9). Observed morbidity and accuracy of prognostic scores For correlation of POSSUM predicted morbidity with observed morbidity as per different classes of Clavien-Dindo scale, a vertical box plot was plotted [Figure 2]. The POSSUM predicted morbidity risk was found to be significantly associated with the observed morbidity (P = 0.001).
Observed mortality and accuracy of prognostic scores ASA-PS IIIE or IVE had 12.7 times higher risk of mortality compared to ASA-PS IE and IIE (P < 0.001). For every unit increase of SOFA, POSSUM, and P-POSSUM score, there was a 50%, 18%, and 17% higher risk of mortality. A positive qSOFA was associated with 9.03 times higher risk of mortality as compared to negative (P < 0.001) [Table 2].
On analysis of ROC, the AUC for the POSSUM, P-POSSUM, and SOFA was 0.85, 0.86 and 0.8829, respectively [Figure 3]. The Youden's index (YI) value was 0.6, 0.6, and 0.89 for POSSUM, P-POSSUM, and SOFA score, respectively [Figure 4]a,[Figure 4]b,[Figure 4]c.
The Hosmer-Lemeshow (HL) goodness of fit test revealed both POSSUM and P-POSSUM models to be a good fit for predicting mortality at 30-days, with small χ2 HL values (POSSUM: χ2 HL statistic = 3.94; df = 8; P = 0.26 and P-POSSUM: χ2 HL statistic = 3.26; df = 8; P = 0.19) [Table 3]. Smaller χ2 HL values suggest good fit, with the data considered to be fitting the model if P > 0.05. The observed mortality was higher than that predicted for the first three of the 20% risk bands, that is, up to 41%–60% risk band.
The COVID-19 pandemic was associated with a significant health care burden in India, with more than 34.5 million infected cases reported till date.[15] We observed a postoperative 30-day mortality rate of 19% in COVID-19 emergency surgical patients. ASA-PS IIIE/IVE and a positive qSOFA were significantly associated with mortality. Further, SOFA, P-POSSUM, and POSSUM scores had a good discriminant value to differentiate between survivors and non-survivors in our COVID-19 emergency surgical cohort. Carrier et al. reported 50% of symptomatic patients with 18% in need of mechanical ventilation and a 30-day mortality rate of 15.9% in 44 COVID-19 emergency surgical patients.[16] The COVIDSurg Collaborative observed a higher mortality of 26% after emergency surgery.[1] In our patient cohort, the 30-day mortality rate was 19% with higher mortality in general/gastrointestinal surgery (83%) followed by neurosurgical (50%), orthopedic (33.3%), sinus (rhino-cerebral mucormycosis) surgeries (13.9%), and lower segment cesarean sections (5%). However, comparisons between different studies are difficult because of different individual patient-related demographics, clinical presentation and pathologies, along with variation in surgical approaches, resources, and overall perioperative care. The clinical presentation of our emergency surgical COVID-19 patients was varied with presence of respiratory, digestive, cardiac, and neurological symptoms. SARS-CoV-2 is known to affect multiple organ systems with a vast variety of symptoms.[17] The strong association between COVID-19-induced severe inflammatory response and ACE-2 receptors expressed in nasal mucosa, bronchus, lung, heart, esophagus, stomach, ileum, kidney, and bladder is reported in literature.[18] However, it is difficult to establish causality with COVID-19 of any symptom other than respiratory. ARDS can result from direct lung damage as in pneumonia, aspiration, or indirect causes like sepsis and pancreatitis.[19] We observed the presence of preoperative ARDS in 17 patients. ARDS was likely due to COVID-19 in the obstetric, mucormycosis, and toe gangrene patients. However, the ARDS present in the abdominal pathologies may be attributed to either COVID-19 or bacteremic sepsis, which in abdominal infection is known to be associated with ARDS.[20] In patients with abdominal pathologies, common inflammatory pathways may cause endothelial damage, inhibit alveolar immunological responses, reduce lung compliance with onset of hypoxemia and ARDS.[20] In our cohort, 94% of the patients tested positive for COVID-19 before surgery. No difference in morbidity or mortality was noted in patients who had tested COVID-19 positive prior to or after surgery. These patients who tested positive within a week after surgery were likely already in the incubation period with ongoing pathophysiological changes, and hence, behaved similarly to patients who had tested positive preoperatively. Patients testing positive for COVID-19 could be susceptible to poor perioperative outcomes due to synergistic immunological dysregulation, a hyperinflammatory response to surgery, and need for mechanical ventilation.[1],[21] Most postoperative complications developed in patients with preoperative ARDS. Postoperative mortality was often secondary to septic shock, ARDS and multiorgan dysfunction in our patients, which could be multi-factorial due to COVID-19 as well as sepsis. Though sepsis may be present as a post-surgical complication, mortality due to postoperative ARDS is rare in only abdominal pathologies, making contribution of COVID-19 likely.[20] The intensive care beds were overwhelmed and few during the COVID-19 pandemic. Thus, ICU discharge was expedited in relatively stable patients to care for sicker patients, though the patients remained hospitalized for duration ranging from 8 to 44 days. Previous studies on COVID-19 surgical patients did not study the performance of prognostic risk indices in prediction of postoperative mortality.[2] The COVIDSurg study observed that ASA-PS grade III–V was an independent risk factor for mortality.[1] ASA grade IIIE and IVE were seen in 77% of non-survivors with hazard ratio of 12.7 for mortality as compared to ASA IE and IIE in our study. SOFA score had a good discriminant function between non-survivors and survivors (AUC 0.89), with 1.5 times higher odds of mortality with every unit increase. Since patients with COVID-19 have an ongoing cytokine storm and systemic inflammatory response, the SOFA score which evaluates six major organ functions was observed to have a better discriminant function.[9] The quick SOFA score (qSOFA) needs just three parameters: respiratory rate (RR) of ≥22 breaths per minute, altered mentation (Glasgow Coma Scale (GCS) <15), and systolic blood pressure (SBP) of <100 mmHg for rapid identification of sepsis.[22] The COVIDSurg study reported that qSOFA score was ≥1 in 62.8% of non-survivors at 30 days after surgery.[1] Increased risk of postoperative ARDS and sepsis was observed after vascular surgery in COVID-19 patients with a positive qSOFA score.[23] We observed that a positive quick SOFA score had a 9 times higher risk of mortality as compared to negative. Both POSSUM and P-POSSUM scores were significantly higher in non-survivors compared to survivors, with good discriminative ability (AUC 0.85 and 0.86, respectively). Further, we found that POSSUM underpredicted postoperative mortality in COVID-19 patients in the lower pentiles of risk. Previous studies in pre-COVID surgical patients concentrating on different specialties have also observed significant variations from the predicted models at lower bands of predicted risk.[24],[25] Strengths of our study are that it is the first to assess the performance of prognostic risk indices for assessment of postoperative 30-day mortality in COVID-19 patients undergoing emergency surgery from the Indian subcontinent. Second, we included only the COVID-19 positive cohort reported to have higher risk of mortality as per previous literature. Third, we were able to complete outcome analysis in all patients and draw a perspective regarding the goodness of fit scores like POSSUM and P-POSSUM in prediction of 30-day mortality in COVID-19 emergency surgical patients. Fourth, we included objective scores like SOFA, POSSUM, and P-POSSUM, calculated using easily available online calculators with prospective data collection, thereby decreasing any error in recording of the data sets. Our study has a few limitations. First, the small sample size stresses upon severe restriction in surgeries, with only the emergent ones done in this pandemic. Second, the comparison with a cohort of non-COVID-19 patients was not done in this study, which limits the understanding of the actual risk attributable to the presence of COVID-19. Third, the clinical presentation, severity of COVID-19, and surgical and anesthetic characteristics of each patient were different. This study may give a risk estimate regarding mortality but ultimately, prognostication needs to be individualized in each patient depending on multiple clinical and surgical factors as well as subtle differences in presentation of similar comorbidities. Fourth, this is a single-center study. However, the data analyzed spans a period of 1.5 years and we were able to find a good discriminant activity of POSSUM, P-POSSUM, qSOFA, and SOFA in predicting mortality. Fifth, the possibility of false positive COVID-19 RT-PCR tests cannot be ruled out. In conclusion, though only few COVID-19 emergency surgical patients were included in our study, SOFA score was observed to have a better risk prediction potential, with good AUC and a higher sensitivity as compared to P-POSSUM and POSSUM. A positive qSOFA and ASA IIIE and IVE were also significantly associated with increased mortality. However, further multicentric studies with inclusion of higher number of patients and a control group of non-COVID-19 patients are needed for better validation of these prognostic scores in COVID-19. Acknowledgements We acknowledge the tireless work of all faculty, resident doctors, nursing staff and other health care professionals in treating COVID-19 patients throughout the pandemic. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]
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