Pathophysiology of risk factors for post operative complications

Age

There is a higher incidence of post-operative complications in elderly patients, when compared to younger age groups.⁴ A systematic review and meta-analysis published in 2018 notes that although more post operative complications are noted after elective surgery in older age groups (age >60 years) with an incidence of 25.17%, it is not the sole prognostic factor responsible for those complications. Frailty was responsible for doubling of the complications in older age group with odds ratio of 2.16.⁵ As per the to the reports of GOSAFE study (Geriatric Oncology Surgical Assessment and Functional recovery after surgery study), frailty is common in elderly patients who undergo cancer surgery. The goal of this study was to gather prospective data on both functional recovery (FR) and quality of life (QoL) in these patients after surgery.⁶

Gender

Genetic, physiological, and environmental factors play an important role in creating health differences between females and males. Gender-related discrepancies in outcomes after a surgery have been reported in many studies. Males are usually seen to have higher mortality rates, after surgeries like lung resection, hip replacement surgery and sepsis, while females experience higher complication rates secondary to endovascular repair of abdominal aortic aneurysms and bear a negative effect on morbidity following cardiovascular procedures and CNS-related complications after surgical procedures.⁷ Females have reduced red cell mass and have lower circulating blood volumes of RBC’s compared to males, and significant amounts of blood loss was noted in females undergoing certain procedure. Thus, there was higher relative loss of red cell mass and higher rates of transfusion in females.⁸

Anemia

From a surgeon’s point of view, anemia is viewed as a non-specific sign for disease associated with low haemoglobin levels. Blood loss leads to decreased blood pressure and thus leads to release of catecholamines. There is vasoconstriction, increase in contractility of cardiac muscles which leads to increased cardiac output and normalizes the oxygen delivery to tissue by increasing the blood flow. Impaired oxygen delivery to tissues leads to membrane instability at cellular level, this sodium (Na⁺) and water flow into the cells and potassium (K⁺) moves out followed by cellular oedema which leads to cell death. During surgery, a fresh wound is created and the anaerobic environment in the wound is augmented by the presence of anaemia. This makes the local conditions ideal for growth of microorganisms, leading to infection of wound and delay in wound healing. An elderly patient is unable to compensate for loss of haemoglobin due to inability to increase cardiac output. This can result in poor tissue perfusion and stroke in such patients or myocardial infarction (MI). However, pre-operative blood transfusion may decrease this risk. Hypoxemia can also be associated with post-operative mental confusion.⁹

It is imperative to know the causes of pre-operative anaemia for appropriate management of anemia, the commonest cause being Iron deficiency worldwide. The other causes include parasitic infestation by either hookworms, malaria and schistosomiasis, pregnancy and gynaecological diseases, anemia associated with chronic renal disease and haemoglobinopathies.⁸ Anemia is defined by WHO on the basis of Hb concentration and has defined various thresholds for Hb and anemia as per age, gender and its severity are graded as mild, moderate or severe As per WHO it was noted that in a case of Iron Deficiency Anemia (IDA), the term “mild” is a misnomer because the anemia is very severe by the time it is detected, and its consequences are not apparent clinically. Also, adjustments of thresholds for level of Hb pertaining to altitude and smoking are necessary.⁸

ICC-PBM (International Consensus Conference on Patient Blood Management) meeting in Frankfurt, stated that “perioperative anemia is an important risk factor for peri-operative morbidity (acute myocardial infarction, ischemic stroke or kidney injury) and hospital and 30-day mortality”. Thus, it is essential to detect as well as classify anemia well in advance of major elective surgery. The leading causes of preoperative anemia include absolute iron deficiency and iron sequestration, whereas surgical blood loss and inflammation lead to postoperative anemia. In February 2018, WHO gave gender and age specific non-anemic values of haemoglobin as described in Table 2.¹⁰

Concept of post-operative anemia

Post-operative anemia can be a consequence of anemia present pre-operatively, anemia due to intraoperative blood loss or due to coagulopathy or phlebotomies in the perioperative period and also due to surgical stress which leads to decreased rate of erythropoiesis due to inflammatory cytokines, decreased uptake of iron from the gastrointestinal tract (GIT) due to inflammation and diminished response of RBCS to erythropoietin. It is also noted that pre-operative anemia renders the patient at increased need of intra-operative blood transfusions and its complications.¹¹

Research data analysis

A retrospective study published by Xu et al. in 2022 in patients undergoing pancreatoduodenectomy (PD), noted that after propensity score matching (PSM) in the groups having anemia the prevalence of postoperative complications was higher especially related to cerebrovascular and cardiac events in these patients. The complications in this particular study were recorded using the Clavien-Dindo Classification system.¹² To understand this further, anemia decreases the oxygen (O₂) carrying capacity of the blood is reduced, thus affecting the myocardial oxygen supply. When this factor gets combined with tachycardia, hypotension and ionotropic supports being used during peri-operative period there is mismatch in O₂ supply and demand, thus leading to myocardial injury in non-cardiac surgeries. The study also reported that the optimal cut-off values of prediction of major post-operative complications in male was 10.45 g/dl and in females was 9.05 g/dl.¹³ A meta-analysis published by Fowler et al. in 2015 confirms that despite the heterogenicity between the studies in the review, pre-operative anemia was associated with poor outcomes after surgery. The meta-analysis has included data from 24 observational studies including both cardiac and non-cardiac surgeries. In patients undergoing cardiac surgeries, anemia association was noted with increase in the risk of stroke with p value of 0.009.¹⁴

Hypoalbuminemia

Patients having malnutrition have a higher rate of morbidity and mortality. Serum albumin (Sr Albumin) level proves to be a good indicator of presence of severity of malnutrition and thus is an indirect indicator for surgical risk. Hypoalbuminemia causes delay in recovery of function of bowel and thus is responsible for complications after gastrointestinal (GI) surgeries. The common complications seen due to hypoalbuminemia are wound infections, anastomotic leak, pneumonia etc.¹⁵

Albumin protects the body from inflammatory processes and also it acts a carrier molecule for the purpose of elimination and distribution of drugs in the body. Hypoalbuminemia can be due to inflammation, damage to hepatocytes, insufficiency of dietary amino acids, decreased synthesis of albumin and increased albumin excretion. It is well known that hypoalbuminemia is an independent risk factor for developing Surgical site infections (SSI’s), in patients undergoing GI surgeries. In a study done on 524 patients of GI surgeries, pre operative hypoalbuminemia, especially albumin levels of <3 g/dl was associated with increase in rate of deep SSI’s compared to Superficial SSI’s. It has also been seen that low albumin levels are associated with poor outcomes in patients having Covid -19 infection.¹⁶

Research data analysis

As per literature, serum albumin level was a much better predictor of sepsis and major infections and thus better in predicting outcomes of surgery compared to other preoperative patient characteristics.¹⁷ As per a study cohort data compiled using the ACS NSQIP database (American College of Surgeons, National Surgical Quality Improvement Program), a pre-operative serum albumin of 3.4 g/dl predicts death in 30-days post-operatively. The secondary outcomes studied which had high odds in relation to hypoalbuminemia were, death, stroke, cardiac arrest, and reoperation.¹⁸ A systematic review of literature published by Joliat et al in 2022 emphasises that serum albumin levels decline post-operatively and this decline of serum albumin levels can be used as a valuable biomarker in predicting outcomes after GI surgeries with a sensitivity of 63% - 84% and a specificity of 61% - 86%. There were total 16 studies included in the review out of which 9 studies recorded a threshold of decline of serum albumin to be in the range of 0.5-1.1 g/dl.¹⁹

Body mass index (BMI)²⁰

From a surgeon’s point of view, obesity has always been considered as a risk factor for post operative outcomes. The common complications seen post operatively due to obesity include respiratory complications like obesity hypoventilation syndrome, sleep apnoea, pulmonary embolism, atelectasis of lungs, pneumonia, etc.; cardiovascular complications like atrial fibrillation especially after cardiac surgeries, and wound related complications like wound dehiscence, SSI’s. The metabolic and immune response of body to any injury or trauma, initiates a response known as “acute phase” response. The activation of this response stimulates the antimicrobial response, reduces the damage to tissues, and promotes healing of wound. In support to this response the protein metabolism shifts i.e., there is increased loss of proteins from the gut, skeletal muscle and connective tissue and an increased synthesis of liver “acute phase proteins”. Whole body turnover of protein increases thus there is increase in nitrogen excretion, which leads to negative nitrogen balance in the body. When uncontrolled and in excess it can lead to loss of lean body mass, decreased immunity, impaired pulmonary function and increase in risk of mortality. Obese patients have decreased efficiency of protein synthesis, and the body undergoes changes which indicate muscle catabolism. They have decrease in “rate of lipolysis per unit fat mass” and increased level of free fatty acids (FFA) in the plasma. This means that obese patients do not use their fat stores effectively and rely on endogenous protein sources. Thus, pulmonary related complications and MOF are more, after major trauma in these patients.

Obesity and wound related complications

The proposed theory for wound dehiscence due to obesity is that “obesity directly effects the traction at the fascial edges at the time of closure and this in-turn increases the risk of wound infections, which can lead to wound dehiscence.” Adipose tissue is relatively avascular in nature thus leads to hypoperfusion of the tissue and also decrease in oxygen tension. The bactericidal action of neutrophils is by oxidative killing of the surgical pathogens. Now this decreased oxygen tension at the surgical site in an obese individual will lead to reduced bactericidal activity of neutrophils, leading to increase in risk of SSI’s. When obesity is present in association with insulin resistance, there is impaired function of macrophages, impaired collagen accumulation, also angiogenic response and production of growth factor is impaired which causes impaired healing of wound and finally there is increase in risk of wound infection.²⁰

Longer operation time in obese individuals is a strong predictor of wound infections post-operatively. Furthermore, elevated levels of blood glucose, impaired immunity and traction at surgical site are also the factors leading to impaired wound healing. The evidence existing regarding the effect of obesity on postoperative complications following gastrointestinal surgery are conflicting. There are studies suggestive of obesity paradox i.e moderate obesity decreases an adverse event, while patients who are underweight have higher propensity to develop complications. Some studies suggest that a patient with obesity is at increased risk to develop surgical-site infection (SSI) and deep venous thrombosis and thromboembolism.²¹

Smoking²²

It is known that smoking has strong association with cancer, pulmonary diseases and cardiovascular diseases. A study done by Yoshikawa R et al. shows that, the risk of complications and that of mortality in the 30 days post operative period may increase due to smoking.²² Smoking can cause poor postoperative outcomes like impaired wound healing, wound infections, and cardiopulmonary complications. It has been noted that, smoking affects the transport as well as production of mucus within the pulmonary tract, ameliorates the immune system, can facilitate pulmonary inflammation thus resulting in respiratory dysfunction and pneumonia. Carbon monoxide and nicotine which are carried by smoking have effects on platelet function and vascular tone thus causing cardiac complications or wound related complications by causing impaired wound healing due to smoking-induced ischaemia. The Japanese Society of Anaesthesiologists have issued guidelines for cessation of smoking perioperatively, which suggest that cessation of smoking at least 4 weeks prior to elective surgery reduce the risk of postoperative complications.”²²

History of previous abdominal surgery

Previous abdominal surgery was noted a risk factor, the rationale for it being that, it leads to more intra-abdominal adhesions thus increase in operative time, as well as postoperative ileus.²³ This is the cause of increased morbidity in patients who have undergone previous abdominal surgery. Other complications of previous surgical scar include wound dehiscence and weakening of the abdominal wall muscles, thus leading to increase in incidence of incisional hernias in post-operative period.