Epidemiology and Long-term Outcomes of Acute Kidney Injury in Adult Patients with Perforation Peritonitis Undergoing Emergency Laparotomy

HIGHLIGHTS

Acute kidney injury (AKI) is common in patients undergoing emergency laparotomy for perforation peritonitis and adversely affects clinical outcomes. The presence of CLD, intraoperative blood loss, and the use of crystalloids and vasopressor increase the odds of developing AKI.

INTRODUCTION

Acute kidney injury is observed in 5.0–7.5% of all hospitalized patients and 40% of them are postsurgical. Major intraperitoneal surgeries contribute to around one-third cases of postoperative AKI in several published literature.^1–4 Postoperative AKI has been studied extensively in the setting of cardiovascular surgery with an incidence of about 30% following cardiac surgery.⁵ The development of AKI increases cost and length of hospital stay and mortality.⁶

Literature on AKI in elective major abdominal surgeries has observed that older age, higher body mass index (BMI), preexisting kidney dysfunction, hypoalbuminemia, use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, higher modified end-stage liver disease (MELD) score, higher revised cardiac risk index (RCRI) score, and higher SAPS II score as major risk factors.⁷

There is an increased risk of developing AKI in secondary peritonitis patients undergoing emergent/urgent surgery and probably contributed by hypotension, volume depletion, sepsis, and use of nephrotoxic drugs. Reported mortality in this cohort is high and around 15–17%.⁸ However, epidemiological data on these patients are lacking. Moreover, these patients may be at risk of long-term kidney dysfunction because of the frequent association of sepsis. Hence, we planned to conduct a prospective cohort study to identify the incidence, risk factors, and long-term adverse renal outcomes of patients undergoing emergency laparotomy.

The primary objective of this study was to know the incidence of AKI on the third postoperative day and secondary objectives were (1) incidence of AKI on the 7th postoperative day, (2) risk factors of AKI, (3) hospital mortality, (4) length of hospital stay, (5) need for renal replacement therapy (RRT), and (6) long-term adverse renal outcome at 3 months in those developing postoperative AKI.

MATERIALS AND METHODS

This cohort study was conducted at All India Institute of Medical Sciences, New Delhi, India from January 2021 to August 2022.

RESULTS

One hundred and forty patients were included and n = 69 patients developed AKI by day 7. Baseline demographic, clinical and laboratory data were reported in Table 1. Patients who developed AKI had lower hemoglobin, higher INR, higher APACHE II score, higher incidence of CLD, lower serum sodium, higher intraoperative blood loss, higher intraoperative hypotension, more use of crystalloids, colloids and vasopressors, and increased duration of anesthesia (Table 1).

On postoperative day 3 (POD 3), according to urine output criteria, 47 (34.3%) patients and as per serum creatinine criteria, 55 (40.1%) patients developed AKI. Out of the patients who developed AKI on POD 3, 41 patients had AKI KDIGO stage I (29.9%), 16 patients (11.7%) had stage II and 4 (2.9%) had stage III. On postoperative day 7, based on urine output (UO), a further 22 patients (16.1%) developed AKI and as per serum creatinine criteria [10 patients (19.1%)]. Out of the patients who developed AKI 18 (13.1%) had AKI KDIGO stage I, 7 patients (5.1%) had stage II and 4 patients (2.9%) had stage III (Fig. 1).

Variables associated with AKI in univariate analysis were initially chosen for inclusion in binary regression model (Table 2). Binary regression model yielded that larger volume of crystalloid [OR (95% CI) 1.00 (1.00–1.00; p = 0.012], intraoperative vasopressor use [OR (95% CI) 7.42 (2.41–22.83); p < 0.001], intraoperative blood loss [OR (95% CI) 1.004 (1.00–1.01); p = 0.003] and presence of CLD [OR (95% CI) 22.4 (1.7–299.3); p = 0.019] were independently associated with AKI.

In this cohort, day 90 eGFR was significantly lower than baseline eGFR [median (IQR) 110 (84–141) at baseline vs 101 (75–118) at day 90; p < 0.001]. Baseline eGFR was similar in patients who had AKI and who didn’t have [median (IQR) 106 (70–143) in AKI group and 112 (95–134) in non-AKI group; p = 0.22]. At postoperative day 90, eGFR was significantly lower in patients who had AKI and who did not have [median (IQR) 80.5 (69–107) in AKI group and 106 (84–123) in non-AKI group; p < 0.001]. Repeated measure of ANOVA reported that there was a significant interaction between eGFR and age (p = 0.004) and between eGFR and baseline APACHE II score (p = 0.022).

Within the study period of 90 days, 18 patients (12.86%) died. Follow-up outcome data are provided in Table 3. Median (IQR) postoperative hospital stay for patients without AKI was 7 (5–10) days and with AKI was 11 (7–20). Median (IQR) postoperative ICU stay for patients with no-AKI was 0 (0–0) and with AKI was 3 (0–6) (Table 3).

DISCUSSION

We have found that nearly one-third and 16% of patients fulfilled the criteria of AKI at postoperative day 3 and day 7, respectively. Larger volume of crystalloid use, intraoperative vasopressor, intraoperative blood loss, and presence of CLD were independent risk factors for postoperative AKI. Patients with postoperative AKI had longer hospital stays and higher postoperative mortality. Follow-up data reported that eGFR declined from baseline to postoperative day 90 and it was associated with both patients’ age and baseline APACHE II score.

Mikkelsen et al. reported that 17.4% of patients developed AKI as per KDIGO criteria, following emergency laparotomy by day POD 7, and around 11% of all AKI was stage III.¹¹ A higher incidence of AKI reported in our study was probably due to the fact that relatively less sick patients were included in the aforementioned study. Though the authors did not report baseline disease severity, only 9% of patients included in that study had a qSOFA >1. The pathophysiology of postoperative AKI is probably multifactorial. We observed that risk factors for postoperative AKI were higher use of crystalloid, intraoperative vasopressor use, intraoperative blood loss, and the presence of CLD. Though, the baseline severity of illness measured by APACHE II score was not an independent predictor in our study, a trend of association was observed.

A retrospective study conducted by Mikkelsen et al. reported that risk factors for postoperative AKI were old age, smoking status, higher quick sequential organ failure assessment (qSOFA), lower performance score at admission, higher ASA class and Charlson Comorbidity Index (CCI). Furthermore, patients who developed AKI had hypertension and diabetes mellitus. Intraoperative peritoneal contamination was also found to be associated with the development of AKI.¹¹ In the previous studies performed in elective surgeries, risk factors associated with AKI were older age, higher non-renal RCRI and SAPS, intraoperative transfusions, comorbid conditions, lower baseline eGFR, longer and complex surgical procedures.^10,12,13 In a prospective observational study conducted by Kheterpal et al., liver disease was an independent preoperative predictor of AKI in their cohort.¹⁴ A recent study from India reported a univariate association between sepsis and AKI in peritonitis patients, which is intuitive.¹⁵ Risk factors of AKI in Indian patients after hepatic resection were reported previously.¹⁶

We observed a decline in eGFR at postoperative day 90; though the eGFR was lower in patients with AKI, it was probably contributed by the older age and higher APACHE II score of the patients also.

Our study has several limitations. First, this was a single-center study and included only a limited number of patients. Second, our follow-up period was restricted to 90 days only, hence, further decline (or recovery) of renal function could not be determined. Third, we used eGFR for renal function monitoring instead of the “24-hour creatinine clearance,” which is considered to be the “gold standard.”

CONCLUSION

We have found that in patients who are undergoing emergency laparotomy for perforation peritonitis, larger volume of crystalloid use, intraoperative vasopressor use, and blood loss were associated with postoperative AKI. There was a decline in eGFR at postoperative day 90 which was probably contributed by the patients’ age and higher disease severity. Postoperative AKI adversely affected clinical outcome in these patients.

ORCID

Pallavi Priya https://orcid.org/0000-0002-0142-9365

Dalim K Baidya https://orcid.org/0000-0001-7811-7039

Rahul K Anand https://orcid.org/0000-0002-7852-1231

Bikash R Ray https://orcid.org/0000-0003-1461-1518

Puneet Khanna https://orcid.org/0000-0002-9243-9963

Asuri Krishna https://orcid.org/0000-0002-1214-0014

Souvik Maitra https://orcid.org/0000-0002-2328-9201

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