Biomarkers for Predicting Complications in Microvascular Flap Surgery. Summary of the Doctoral Thesis

Abstract

Microvascular flap surgery has secured its place in reconstructive surgery as an important technique for correcting various tissue defects. Despite substantial progress in surgical techniques and reduction of complication rates, flap loss remains a challenge. This research aimed to outline new avenues for improving outcomes and to examine novel nutritional, inflammatory, and immunological biomarker models for predicting complications in microvascular flap surgery. The first part of the research involves a narrative literature review that analyses 80 studies in PubMed, Scopus and Web of Science published from 1 January 2007 to 1 July 2024. The aim of the first part was to outline novel avenues for best practice and provide an outlook for further research of anaesthesia and perioperative care concepts in microvascular flap surgery. The results of the narrative review indicated that the assessment of nutritional status, hypoalbuminemia, chronic inflammation, and hypercoagulability assessment currently lack sufficient data and are highly promising avenues for further research. The first study of the prospective observational part includes 72 adult patients undergoing elective microvascular flap surgery. The aim of this study was to assess the predictive value of the Controlling Nutritional Assessment (CONUT) score for complications in microvascular flap surgery. Blood samples for full blood count, total plasma cholesterol, and albumin levels were obtained on the day of surgery prior to initiation of crystalloids. The serum albumin concentration, total peripheral lymphocyte count, and serum total cholesterol concentration were used to assign the CONUT score. The CONUT score had an AUC of 0.813 (0.659–0.967, p = 0.012) for predicting complications other than true flap loss due to vascular compromise. A CONUT score > 2 was indicated as optimal during cut-off analysis (p = 0.022). Patients with flap complications had a longer duration of hospitalisation (13.55, 10.99–16.11 vs. 25.38, 14.82–35.93; p = 0.004). Our findings indicated that the CONUT score has considerable predictive value for minor flap complications in microvascular flap surgery but was not predictive of true flap loss. The second study of the prospective part aimed to evaluate the Fibrinogen-to-Albumin ratio (FAR) for predicting complications in microvascular surgery. It included 130 adult patients undergoing elective microvascular flap surgery. Preoperative blood draws for analysis of plasma fibrinogen and albumin were collected on the day of surgery prior to crystalloid infusion. Binary logistic regression revealed that patients with FAR < 0.08 and FAR < 0.06 had increased odds of flap haematoma or flap loss (OR 3.68, 1.04–13.03, p = 0.044 and 6.01, 1.71–21.08, p = 0.005). Patients with FAR > 0.10 had increased odds of minor flap complications (OR 5.47, 1.33–22.50, p = 0.019). Patients with FAR < 0.06 had increased odds of flap complications (OR 4.71, 1.27–18.03, p = 0.021). FAR > 0.10 also increased the odds of flap complications (OR 3.09, 1.08–8.81, p = 0.035), implying a U-shaped link. The third study of the prospective part evaluated the link between von Willebrand factor antigen (vWF:Ag) and flap complications in 88 adult patients undergoing elective microvascular flap surgery. Preoperative blood draws were collected on the day of surgery prior to crystalloid infusion. The plasma concentration of vWF:Ag, albumin, neutrophil-to-lymphocyte ratio (NLR), interleukin-6, C-reactive protein (CRP) and fibrinogen were determined. vWF:Ag levels were higher in true flap loss when compared to patients without complications (217.94 IU/dL, 137.27–298.45 vs. 114.14, 95.67–132.71, p = 0.001). Regression analysis revealed an association between vWF:Ag and true flap loss a cut-off point of 163.73 IU/dL (OR 70.22, 10.74–485.28, p = 0.043). Increased vWF:Ag concentrations were linked to increases in plasma fibrinogen (p < 0.001), CRP (p < 0.001), interleukin-6 (p = 0.032), and NLR (p = 0.019). The findings of this study indicate that preoperative plasma vWF:Ag concentration is linked to biomarkers of inflammation, and the selected cut-off provides a viable model for predicting complications in microvascular flap surgery. The fourth study of the prospective part aims to evaluate the viability of tumor necrosis factor beta-1 (TGF-?1) for predicting microvascular flap complications. This prospective observational cohort study included 173 individuals who underwent elective reconstructive microvascular flap surgery. All patients who had true flap loss or secondary flap complications (n = 22) were included in the complication group. An equal number of patients with no complications (n = 22) were selected from the overall cohort using simple randomisation to form the 44 patient cohort to match the available sample count for laboratory analysis. Preoperative blood draws for analysis were collected on the day of surgery before crystalloid infusion. Postoperative blood draws were collected after surgery before leaving the operating room. Preoperative and postoperative plasma concentration of TGF-?1 as well as preoperative parameters such as full blood count, albumin, interleukin-6, total protein, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, CRP, and fibrinogen, were determined. Increased postoperative TGF-?1 was positively linked to preoperative plasma fibrinogen (p = 0.020), plasma CRP (p = 0.021), haematocrit (p = 0.039) and haemoglobin (p = 0.009). Postoperative change of TGF-?1 was higher in patients with true flap loss when compared to patients without complications and patients with minor flap complications (0.403 log10 of ng/ml, 0.024–0.782 vs. 0.157, 0.029–0.285 vs. ?0.089, ?0.233–0.056, p = 0.002). Multivariate regression analysis revealed that an increase in postoperative change of TGF-?1 increases the odds of true flap loss (OR 2.028, 1.185–3.471, p = 0.009). This research has developed models of nutritional, inflammatory, coagulation and immunological biomarkers to predict complications in microvascular flap surgery. It has also uncovered important new insights into the pathophysiology of these complications and expanded our understanding of preoperative assessment. These advancements may improve outcomes for patients undergoing microvascular flap surgery.