*3.1. Demographic Data and Preoperative Evaluation*

A total of 345 patients, aged between 18 and 91 years, were admitted in emergency with the diagnostic of acute cholecystitis during January 2018 and December 2019. A total of 12 patients (3.47%) did not undergo cholecystectomy during the same hospital admission and were excluded from the statistical analysis. In one case (0.28%), a man aged 87, with severe cardiac insufficiency and sepsis (ASA IV), emergency cholecystostomy was performed. Drainage of the bilious-purulent content of the gallbladder allowed recovery in a case in which general anesthesia was considered not appropriate due to high risk of death. Conservative management was used in 11 cases (3.18%). Four cases refused surgery (aged between 42 and 83 years), while in seven cases cholecystectomy was postponed by the surgeon for various reasons (Table 2).

**Table 2.** Demographic and clinical data of non-operated patients.


\* hypertension—Blood pressure (BP) of 22 mmHg at admission. As the patient responded to medical therapy for acute cholecystitis, he was referred to a cardiologist and asked to return for elective surgery, under adequate medication. \*\* BMI – body mass index.

> A total of 333 patients (96.54%) underwent emergency cholecystectomy and were further included in the statistical analysis. The distribution of patients follows a multiple peak pattern, suggesting the overlay of multiple populations (Figure 1).

**Figure 1.** Age distribution of patients with emergency cholecystectomy for acute cholecystitis in the study group (*n* = 333).

There were no statistically significant differences in terms of gender distribution in the four subgroups (Table 3). Presentation at more than 72 h after onset was considered a sign of severity of the level of local inflammation according to the Tokyo Guidelines. In the study group, there was a upward trend correlated with age and surgery after 72 h from onset, confirmed by the Linear-by-Linear association test (*p* = 0.007).


**Table 3.** Demographic and preoperative data in the 4 age-subgroups.

Footnote: (1) Test of Linear-by-Linear Association; (2) Fisher's exact test; ASA PS: American Society of Anesthesiologists Physical Status Classification; TG13/18: Tokyo Guidelines classification risk; CCI: Charlson Comorbidity Index. \*\*\* described according to Common Guide of diagnostic and treatment of Acute Cardiac Insufficiency of European Society of Intensive Therapy and European Society of Cardiology: (i) Aggravated preexisting cardiac insufficiency (edema of the lower limbs, congestion); (ii) Hypertensive Cardiac insufficiency (high BP, tachycardia, signs of vasoconstriction); (iii) Pulmonary acute edema: acute respiratory disfunction, with tachypnea and orthopnea, SaO2 < 90% before oxygen administration; (iv) Acute coronary syndrome; (v) Cardiogenic shock: hypotension requiring vasopressor medication, signs of organ hypoperfusion, with oliguria.

> The moderate forms (TG 13/18) were the most frequent in all age groups. However, the statistical analysis showed a tendency for the mild forms to decrease with age, with a corresponding increase in the severe forms with organ/system decompensation (Figure 2),

with statistically significant differences being observed between group A on the one hand and groups C and D on the other hand (*p* < 0.001). The same differences were observed for the leukocytes > 18,000/mmc and fibrinogen > 400 mg/mL.

**Figure 2.** Boxplot representation of age distribution by Tokyo Guidelines TG13/TG18 Classification.

The age of 65 represents a statistically significant demarcation limit in terms of associated comorbidities and anesthetic-surgical risk. CCI correlates well with age (Spearman rho 0.462, *p* < 0.001). In groups C and D compared to groups A and B, there were significantly fewer patients with ASA PS risk I and significantly more patients with ASA PS ≥ 3, with the increase in the ASA score with age being confirmed by the Linear-by-Linear association test (*p* < 0.001).

The incidence of signs of acute cardiac insufficiency at admission significantly increased with age, from 2.5% in group A to 44.1% in group D. Similar correlations were found with creatinine levels > 1.2 mg/mL, an expression of a pre-existing age-related limitation of renal function, with decompensation in the context of systemic inflammation and sepsis. There were only five cases with INR > 2. It correlated with chronic anticoagulant therapy for cardiovascular associated comorbidities.
