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Review article
DOI: 10.1016/j.acci.2020.05.001
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Disponible online el 20 de Junio de 2020
Sepsis after cardiac surgery: The clinical challenge. Review article
Sepsis en posquirúrgico cardiovascular: un reto clínico. Artículo de revisión
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Diana Ávila Reyesa,
Autor para correspondencia
diana.avila@utp.edu.co

Corresponding author.
, David Ricardo Echeverry Piedrahitab,c, Mateo Aguirre Flórezd
a Medicina Crítica y Cuidados Intensivos, Universidad Tecnológica de Pereira, Colombia
b Departamento de Medicina Crítica y Cuidados Intensivos, Docente y Coordinador Académico del Programa de Postgrado de Medicina Crítica y Cuidados Intensivos, Universidad Tecnológica de Pereira, Colombia
c Asociación Colombiana de Medicina Crítica y Cuidado Intensivo (AMCI regional Eje Cafetero), Colombia
d Facultad de Ciencias de la Salud, Programa de Medicina, Universidad Tecnológica de Pereira, Colombia
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Abstract
Introduction

Sepsis continues to be a clinical condition with an ostensibly high mortality despite efforts in early detection and therapeutic interventions, and its incidence in the post-surgical cardiac surgery patient is relatively low. However, when sepsis or septic shock develops in this scenario, it has a negative impact on the results. Regardless of the procedure performed, the success of the outcomes depends on the optimal postoperative care in the Intensive Care Unit, in order to improve the results and to have an effect on the morbidity and mortality.

Objectives

To carry out a review of sepsis in the scenario of the post-surgical cardiovascular patient, its pathophysiology, risk factors, integral management, and the results of different therapeutic strategies in the light of current evidence.

Materials and methods

A search was conducted in the main scientific databases (Web of Science/Scopus/PubMed/SciELO/Lilacs/Google Scholar) for review articles of sepsis in cardiac surgery, as well as studies that included targeted treatments, and antibiotic prophylaxis in this clinical context.

Results

Bibliographic references were found in databases from 1996 to 2019.

Conclusion

Sepsis after cardiac surgery is a rare event. There are no different definitions for this group of patients and there are difficulties in diagnosis since the manifestations of septic shock can be confused with the normal postoperative course. Different prevention strategies for postoperative infections are recognized in clinical practice guidelines.

Keywords:
Cardiovascular infections
Cardiac surgery procedures
Sepsis
Shock
Critical care
Resumen
Introducción

La sepsis continúa siendo una condición clínica con una mortalidad ostensiblemente alta a pesar de los esfuerzos en la detección temprana y las intervenciones terapéuticas, y su incidencia en el paciente posquirúrgico de cirugía cardiaca es relativamente baja, sin embargo, cuando se desarrolla sepsis o choque séptico en este escenario, tiene un impacto negativo en los resultados. Independientemente del procedimiento realizado, el éxito de los resultados depende de la atención postoperatoria óptima en la unidad de cuidados intensivos, con el fin de mejorar los resultados y obtener un impacto en relación con la morbimortalidad.

Objetivos

Realizar una revisión sobre la sepsis en el escenario del paciente posquirúrgico cardiovascular, su fisiopatología, los factores de riesgo, el manejo integral y los resultados de diferentes estrategias terapéuticas a la luz de la evidencia actual.

Materiales y métodos

Se realizó una búsqueda en las principales bases de datos científicas (Web of Science/Scopus/PubMed/SciELO/Lilacs/Google Scholar) sobre artículos de revisión de sepsis en cirugía cardiaca, y estudios que incluyeron tratamientos dirigidos y profilaxis antibiótica en este contexto clínico.

Resultados

Se encontraron referencias bibliográficas en bases de datos desde 1996 hasta 2019.

Conclusión

La sepsis después de la cirugía cardiaca es un evento raro, no existen definiciones diferentes para este grupo poblacional y hay dificultades en el diagnóstico dado que las manifestaciones del choque séptico se pueden confundir con el curso normal del postoperatorio. Se reconoce en las guías de la práctica clínica diferentes estrategias de prevención para las infecciones postoperatorias.

Palabras clave:
Infecciones cardiovasculares
Procedimientos cirugía cardiaca
Sepsis
Choque
Cuidado crítico
Texto completo
Introduction

Sepsis continues to be a clinical condition with ostensibly high mortality despite efforts in early detection and therapeutic interventions,1 and its incidence in the post-surgical cardiac surgery patient is relatively low, however, when Sepsis or septic shock develops in this scenario, it has a negative impact on the results.2

In the United States, it is estimated that cardiac surgical interventions, which include aortocoronary bypass graft (CABG), replacement or repair of heart valves and aortic procedures, represent one of the most common categories of all surgeries performed per year, generating a direct annual cost of more than 20 billion dollars, which represents 1–2% of health care costs.3 Forms of surgical site infection (ISO) include mediastinitis and infection of the sternal wound. The average ISO frequency varies from 0.35 to 8.49 per 100 surgeries.4

From the epidemiological point of view, the appearance of sepsis and in the post-surgical period of cardiac surgery is a rare event with a reported prevalence between 0.39% and 2.5% but with mortality ranging between 65 and 79%.2 In a study published in 2017 that included a total of 2477 patients undergoing cardiac surgery, deep sternal infection or mediastinitis was reported as one of the first five complications found, which also raised the need for reintervention with important implications on the results of patients concerning to mortality5

The infections most frequently found in the postoperative period are pneumonia, bloodstream infections, C. difficile colitis and to a lesser extent provide urinary tract infection, and after hospital discharge, endocarditis and percutaneous infection associated with devices6,7

In a study published in 2018 that included 2230 post-surgical cardiac surgery patients found that sepsis, determined by the third definition published in the 2016 guidelines,8 was tested in 4.8% patients.9 In this study it was concluded that although the incidence of sepsis was relatively low, there is a direct relationship between the appearance of sepsis and septic shock with increased morbidity, mortality, days of mechanical ventilation requirement, ICU stay and hospital stay.9,10Given the change in the population pyramid, more and more interventions have been seen in the elderly population, which presents greater comorbidities, require more complex and prolonged cardiac procedures, which leads to greater risks of complication during the post-surgical period.11,12 It is described that elderly patients also have impaired immunity due to immunosenescence, which leads to an increased risk of developing sepsis.13 Antimicrobial prophylaxis in cardiac procedures reduces the appearance of ISO up to five times14

Regardless of the procedure performed, the success of the results depends to a large extent on the optimal postoperative care in the Intensive Care Unit (ICU), since most preventable deaths in the immediate postoperative period are detected in this room and it is necessary of the specialist in Critical Medicine have the knowledge for the early detection of complications, and take early measures in this regard, in the company of the cardiovascular surgery team,15 to improve the results and obtain a positive impact in relation to reducing morbidity and mortality.16,17

In this review, the presentation of sepsis in post-surgical patients of cardiac surgery, its pathophysiology, the diagnostic approach, and the therapeutic management to be performed in adult patients are analyzed.

Definition of sepsis in patients subdued to cardiac surgery

The definitions of sepsis and septic shock have also changed throughout history until the third definition of sepsis is known. In 2001, the systemic inflammatory response syndrome (SIRS) was defined as the presence of two or more anomalies including in the criteria body temperature, heart rate, respiration, or white blood cell count. Sepsis required the presence of two or more SIRS criteria, coupled with a suspected or documented infection.18 However, since the development of SIRS and its progression to sepsis and septic shock, there are complex biological factors and there are still controversies both in the understanding of its pathophysiology, definition, diagnosis and therapeutic approach.19–21

There is currently a definition of sepsis and septic shock for the general scenario 1, however, in the post-surgical scenario of cardiovascular surgery, there are no definitions adjusted to the physiological changes of the procedure, or the diagnosis Differential with Vasoplegic Syndrome 22,23or low cardiac output,24 conditions that could be present in the patient undergoing cardiac surgery without the presence of infection and that make it difficult early detection of sepsis.

Pathophysiology of sepsis in patients submitted to cardiac surgery

The pathophysiology of sepsis involves a complex interaction between several molecular pathways, pro-inflammatory responses, cytokine release, activation of the coagulation cascade, complement system, and cellular components of inflammation.25 Studies show that a percentage of the population, when faced with the infectious process, presents deregulation in that response, in which the pro-inflammatory and anti-inflammatory processes take place concomitantly.26 At the molecular level, the immune response begins when pattern recognition receptors (PRRs) on the surface of host immune cells recognize pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS) and associated molecular patterns with danger (DAMPs), which are released in response to inflammatory stress, triggered by surgical trauma or cardiopulmonary bypass 27Toll-like receptors (TLR) play a central role in the inflammatory response since they control numerous descending pathways.28 The inflammatory response is closely interconnected with the activation of the coagulation cascade and the fibrinolytic system, also mediated by the endothelial lesion characteristic of the septic process, and the alteration of the functioning of coagulation factors a systemic level, which translates into the development of disseminated intravascular coagulation (CID); recognized factor as an independent predictor of organic failure and mortality in the cardiovascular surgery patient scenario 29On the other hand, in patients during cardiac surgery, the complement system is activated by several mechanisms and its activation is involved in the inflammatory response Previously, it was mentioned that the release of endotoxins activates the complement through the alternate pathway, which leads to the subsequent release of proteases and oxygen free radicals, the consequence of which is the increase in the endothelial lesion. When the mechanisms are perpetuated and significant tissue hypoperfusion occurs at the microcirculation level, it is recognized that the progression to the syndrome of multiple organic dysfunctions becomes uncontrollable (SDOM).30

The effects of extracorporeal circulation on the physiology of the organism have been established from the moment of the arrest related to multiple factors that directly influence these changes, such as the contact of the blood with the extracorporeal circulation membrane, the change from the pulsatile flow to non-pulsatile flow, the decrease in temperature, hemodilution, surgical trauma and the use of anticoagulants, added to the short circuit or cardiopulmonary shunt, changes caused by ischemia-reperfusion; factors that influence the activation of complex pathways that generate a systemic inflammatory response.13,31–33 This activated inflammatory response leads to the development of variable levels of immunosuppression, which conditions a greater susceptibility to the development of infections,34,35 all this added to other risk-enhancing factors 36During the phenomena of ischemia-re-perfusion in cardiac surgery, changes have been seen at the intestinal level in relation to an increase in endothelial permeability which generates bacterial translocation, a release of endotoxins that when it enters the circulation induces a systemic response, which can cause systemic damage37–39

Etiology of sepsis

Cardiac surgery patients present the same infections in the post-surgical period as the general population, with the lung being the first source, followed by infections associated with venous access, urinary tract infection and surgical site infections40

Gram-positive microorganisms such as Staphylococcus aureus, Coagulase-negative staphylococci (CoNS) cause approximately 60% of the ISO after cardiovascular procedures. Gram-negative microorganisms such as Enterobacteriaceae spp., Pseudomonas spp., and Acinetobacter spp., are less common pathogens in this clinical scenario and when present, they are more frequently related to patients who have undergone grafts with the saphenous vein.4

A study published in 2012, with a total of 10,522 patients undergoing cardiac surgery, revealed that mortality depended on the type of pathogen, finding that Staphylococcus aureus and Gram-negative bacteria infections are associated with a higher mortality than patients with infections caused by other types of microorganisms. In this study, the presence of a major postoperative infection was found in 3.2% of the patients, Staphylococci were isolated in 52.5%, Gram-negative bacilli in 24.3% and other pathogens in 23.2%. Obesity, previous coronary bypass surgery, emergency surgery, renal failure, immunosuppression, heart failure and peripheral/cerebrovascular disease were associated with the development of postoperative infections, increasing hospital stay and mortality.41

Another study published in 2014 that included 5158 cardiac surgery patients revealed that almost 5% of patients experienced major postoperative infections.42 Among the typical infections, pneumonia was the first focus, followed by bloodstream infections and Clostridium difficile colitis, which represent 79% of all major postoperative infections. Superficial surgical site infections (ISO) were less frequent and interestingly, it was found that 45% of all postoperative infections occur after hospital discharge. The deep ISO are those stratified as mediastinal infections that include mediastinitis, pericarditis and myocarditis, have a relatively low incidence, calculated in 0.25–5% of patients undergoing cardiac surgery, however it is a complication that has a great impact on clinical outcomes of patients because they require surgical reintervention treatment for focus control, prolonged time of antibiotic therapy, hospital readmissions and increased morbidity and mortality.43,44 Infections significantly affect survival, prolonged hospitalization or readmission, which significantly influences the costs of health care.45

Depending on the type of infection, the most frequently found germs are different and in this sense the production of cultures is a sine qua non condition.

Risk factors of sepsis in cardiac surgery

The hospital stay prior to surgery, the use of antibiotics, invasions, the type of procedure and duration, in addition to infectious complications during medical care can lead to the development of sepsis and septic shock of the post-surgical cardiovascular surgery patient.9 Pneumonia associated with health care or associated with ventilator (NAV) is a frequent complication in the post-surgical period of cardiovascular surgery, defined as the presence of pulmonary infection after 48h of the onset of mechanical ventilation, which determines the development of sepsis and is a prognostic factor of ICU stay and morbidity and mortality.46 Prolonged mechanical ventilation for more than 7 days and/or the need for tracheostomy increases the risk of sepsis, ICU stay and mortality.47 In a systematic review and meta-analysis published in 2015, it was concluded that, within NAV prevention strategies, the implementation of selective oral or digestive decontamination with systemic antibiotic prophylaxis can reduce the incidence of infection in critical patients.48

The objective of a study of 173 patients was to evaluate the efficacy of selective digestive decontamination, without parenteral antibiotics for the prevention of pneumonia associated with mechanical ventilation, concluding that this measure can reduce the incidence of VAP in high-risk patients after Major cardiac surgery, without a significant influence on the intestinal flora.49 More studies are required in this specific population to give conclusions on the implementation of this measure.

The ISO correspond to sterile infections and mediastinitis that significantly increase costs, days of care, mortality and correspond to a quality measurement factor in medical care.46 Risk factors for ISO after cardiac procedures include pre-existing peripheral chronic or vascular obstructive pulmonary disease, heart failure, grafts with the internal mammary artery, a greater number of grafts and documented nasal colonization by Staphylococcus aureus. Several studies have shown that diabetes mellitus is an important risk factor for the development of sepsis in patients with cardiac surgery 50and concomitantly it has been found that the increase in blood glucose levels and the variability of they are directly associated with a poor clinical outcome 51,52Due to the poor results and the direct relationship of hyperglycemia as an independent mortality factor and development of deep sternal wound infection, they have been implemented management strategies with insulin infusion both intraoperatively and postoperatively in cardiac surgery 12,53

In a study of 3249 patients undergoing different types of cardiac surgery including isolated coronary artery bypass graft (CABG), repair or replacement of isolated valve, combined valve procedures and CABG, 122 infections of the sternal wound were detected (3, 8%) in 3249 patients: 74 of 1857 patients (4.0%) after CABG, 19 of 799 (2.4%) after valve operations and 29 of 593 (4.9%) after combined procedures. In patients with CABG, bilateral removal of the internal thoracic artery, the duration of the procedure that exceeded 300min, diabetes, obesity, chronic obstructive pulmonary disease and female sex were independent predictors of sternal wound infection. In conclusion, the risk factors for sternal wound infections after cardiac surgery are also related to the type of surgical procedure.54

Another risk factor related to the development of infections and sepsis in cardiac surgery is the administration of blood products.55 Restrictive transfusion strategies with a defined threshold between 8g/L and 10g/L,56 could reduce the risk of postoperative complications, including infection transmission,57 without increasing the risk of mortality in cardiac surgery.

The number of invasions is related to the risk of sepsis, especially bloodstream infections.9

Tools for predicting the risk of developing infection in this population have been developed. In a study of 2020 patients published in 2019, they used the IRIC SCORE, which is a two-variable scoring system for pre-operative stratification of cardiac surgery patients according to their ISO risk after surgery. The proposed tool outperforms other commonly used scoring systems and could be used to define prophylaxis requirement with preventive antibiotic treatment and closer monitoring of high-risk patients.58

Regardless of the possible applications of IRIC, the most efficient management of patients requires the ability to use, in addition to the scales, comprehensive analysis of the clinic, biomarkers and cultures in clinical decision making. No risk scale is superior to the clinician's criteria to the patient's bedside.

Diagnosis of sepsis in cardiac surgery

The diagnosis of sepsis is mainly based on clinical recognition and detection of crop-based pathogens. However, it is recognized that the result of the cultures does not interfere in the early start of the therapeutic approach with broad-spectrum antibiotics in the first hour, taking into account that the results of the cultures can take up to 48h and are negative even in the 30% of cases.1 In post-surgical cardiac surgery patients, cultures may be altered and falsely negative due to the use of peri-operative antibiotic prophylaxis,12 in addition to the relationship between the sepsis produced by endotoxins in this scenario.13 As mentioned, the physical examination of the patient with sepsis in the postoperative period of cardiac surgery is nonspecific and is often confused with other complications of surgery or with changes related to the use of extracorporeal circulation or the anesthetic effect.59 In this sense, the use of molecular panel tests in patients with high suspicion of sepsis, have an important place in clinical practice, in addition to apparently having a good cost-effectiveness relationship in the emergency department.60 The clinical manifestations of both infection and organic dysfunction can be very subtle and vary among patients, depending on multiple factors, such as the initial site of infection, the causative pathogen, bacterial load, virulence level, patient's previous nutritional status, the onset of acute organic dysfunction, the underlying comorbidities, as well as the time of initiation of treatment.61 In the surgical patient, this is even more complex because many of the initial symptoms of sepsis Postoperatively can be easily attributed to common postoperative changes as mentioned, and in this sense the challenge is early diagnosis to achieve interventions that impact patient outcomes.59

Biomarkers

Within the biomarkers and molecular diagnostic tools in sepsis, more than 170 biomarkers have been studied,62 however, these biomarkers are problematic in this scenario, since surgical intervention per se causes an increase in expression of acute phase proteins, for example, the level of C-reactive protein (CRP) increases during the postoperative period after major surgery, in the absence of infection.13 Although the CRP is elevated in patients of major surgery, an association has been established with the tendency of its elevation rather than with an isolated data. In a study published in 2014,63 which included 151 patients, 32% of whom were post-surgical cardiovascular surgery, it was found that persistently elevated levels above >100mg/L four days after the procedure, They are indicative of active infection.

Procalcitonin

Procalcitonin (PCT) is a pro-hormone synthesized by the C cells of the thyroid gland, and has a place for the differential diagnosis of the infectious process in several clinical settings, with pneumonia being the most studied. In patients with coronary bypass heart surgery (Bypass) it has been found that the serum PCT concentration has a peak on the first postoperative day and subsequently drops. In a prospective study of 97 patients 64postoperatively of cardiovascular surgery, a serum PCT concentration>10ng/ml was reported to be highly indicative of septic shock. Later in 2017, a retrospective study was published in China that included 82 patients undergoing cardiac surgery with Bypass.65 The objective of the study was to determine the value of Procalcitonin (PCT) as an early marker of postoperative infection after of cardiac surgery with cardiopulmonary bypass. The results analyze that in the presence of SIRS and together the elevated levels of PCT in plasma were correlated with evidence of infection in the early postsurgical period. The level of plasma PCT exceeded the cutoff value at different time points, suggesting an infection, and it is useful to predict the onset of infection early after surgery. So far there is no large study, nor are there recommendations in this population regarding levels of Procalcitonin or protocols for its implementation that allow us to confirm the infectious process in the post-surgical period, and perhaps the most accepted scenario is to direct the treatment Procalcitonin-based antibiotic to save days of antimicrobial treatment and avoid resistance.1

Other studies suggest the usefulness of endotoxin screening tests, however, at the moment there are no recommendations in this regard in the guidelines of post-surgical cardiac surgery management.13

In a small 2009 study of 32 cardiac surgery patients undergoing bypass, it was shown that a partial time of activated thromboplastin, analyzed by the biphasic waveform (BPW), was able to discriminate between sepsis and SIRS with a sensitivity 100% and a specificity of 93%.66

Presepsin

Presepsin (PSEP) soluble subtype of CD14 or sCD14-ST is a complex product of CD14 cleavage that is released into the general circulation and automated rapid quantification is currently available. Circulating levels of PSEP can be perceived as a control of activated monocyte-macrophages in response to pathogens. It represents a biomarker of the initial phase of systemic infection. A pilot study of 50 patients demonstrated its diagnostic value and prognosis in sepsis in the emergency setting67

It is not known if presepsin can be used to stratify risk in elective cardiac surgery. In a prospective study of 856 cardiac surgery patients, the utility of presepsin for risk stratification was determined, concluding that high preoperative plasma concentration is an independent predictor of postoperative mortality. Presepsin also provided better discrimination than cystatin C, the N-terminal prohormonal natriuretic peptide or procalcitonin.68 Another study mentions its prognostic utility.69 A study published this year, of 122 cardiac surgery patients, aimed to assess the levels of presepsin and procalcitonin to predict adverse postoperative complications and mortality concluding that both biomarkers appear to have a comparable predictive value for renal, cardiovascular and respiratory outcomes in heart surgery patients In addition, presepsin has a better predictive value for hospital mortality, at 30 days and 6 months.70

Interleukin 6

Interleukin (IL)-6 is a pleiotropic inflammatory cytokine with both pro and anti-inflammatory abilities, produced by different cells and tissues, such as leukocytes, adipocytes and endothelium. This cytokine is a reliable biomarker of cardiac dysfunction, occurrence of atrial fibrillation, cardiac myxoma with recurrence, metastasis or remote embolization and atherosclerotic processes. In cardiac surgical patients, the expression of IL-6 reflects the inflammatory process in relation to anesthesia, surgical trauma and perioperative complications. It also predicts postoperative cardiac function and complications, such as infection, atrial fibrillation, cardiac dysfunction and recurrence or myxoma metastasis. The development of new therapeutic agents for the elimination of IL-6 could improve results by inhibiting apoptotic myocardial processes.71 The results of a study of 23 patients suggest that patients over 70 years old undergoing cardiac operations have higher levels of IL-6. The increase in circulating IL-6 in elderly patients can induce a pro-inflammatory state that can lead to an increase in mortality and morbidity.72 Another study of 122 cardiac surgery patients evaluated the ratio of concentrations. of procalcitonin and interleukin-6 in the results. They were measured on the second postoperative day, and the results suggest that PCT levels are related to outcomes in relation to renal function, and IL-6 is a predictor of mortality 73Larger studies are needed to define the role of IL-6 and define its routine use in this clinical scenario.

Treatment of sepsis in the postoperative cardiac surgery

Cardiac surgery patients, which are complicated by postoperative sepsis, represent a particularly challenging patient population, due to their hemodynamic commitment, typical of the intervention that makes it more difficult to obtain hemodynamic stability and adequate tissue perfusion.2,59 Campaign guides surviving sepsis, emphasize that early diagnosis, aggressive resuscitation, adequate antibiotic therapy, source control and organic support are the key elements of sepsis management.1 However, although the guidelines may have improved sepsis management in the general population, they do not provide guidance to specific patient populations. Particularly in the post-surgical cardiac patient, the clinical manifestations can be very subtle and difficult to recognize, since they are easily confused with common postoperative complications.74

The most recent evidence-based guidelines for the treatment of sepsis and septic shock were published in 2018.1 In accordance with the therapeutic guidelines, initial water resuscitation, adequate antibiotic therapy, source control and individual organ support are recommended. The elements of care consist of seven objectives: four will be completed within the first 3h and three will be completed within 6h. Septic patients should be treated with broad-spectrum antibiotics within the first hour after diagnosis.75,76 Ideally, the initial antibiotic treatment should be administered after blood cultures have been taken, although their onset should not be delayed by taking them. It has been shown that inadequate antibiotic treatment or its delayed onset leads to a dramatic increase in mortality.13

Volumetric resuscitation

Resuscitation with liquids is considered the first step to restore tissue perfusion and crystalloids are recommended instead of colloids, taking into account that approximately 50% of hemodynamically unstable patients respond to fluid therapy.77 The direct relationship between volume overload and poor results has also been determined, with increased mortality,78 with a higher risk in patients who have cardiovascular disorders.79 This measure requires monitoring volumetric management using dynamic measures of preload assessment to determine which patients are responders to volume and who do not benefit from expansion with crystalloids, also considering static variables and clinical evaluation integral of the critical patient.80,81

Vasoactives

Sepsis-induced heart dysfunction is common and patients who have undergone cardiac surgery are particularly susceptible to this complication or they may already have preoperative myocardial insufficiency.2

Norepinephrine continues to feel the first line of management in this scenario, followed by vasopressin in patients who do not respond to catecholamines.1 For patients who remain hypotensive after resuscitation with liquids and who have low cardiac output, inotropic therapy with dobutamine can be considered, taking into account the risk of arrhythmias in the post-surgical cardiac surgery patient. It has been shown that, due to the manipulation of the atrium during the surgical procedure, there is a high risk of developing arrhythmias, particularly atrial fibrillation.82 Dobutamine increases cardiac output, but also increases myocardial oxygen consumption, which can result in myocardial ischemia and ventricular dysfunction.13 Levosimendan is an inotropic agent, which acts as a calcium sensitizer, increasing cardiac output without increasing oxygen consumption. A meta-analysis published in 2012 that included a total of 45 clinical trials with 5480 patients, showed a significant reduction in mortality and length of hospital stay in patients with cardiac surgery who received treatment with levosimendan, compared to dobutamine or the placebo.83 Other studies have demonstrated a hemodynamic improvement in patients with sepsis who received levosimendan, in addition, the cardioprotective effects and the reduction in mortality in critical patients are postulated.13 Similar results were found in a 2015 meta-analysis of seven randomized clinical trials that included a total of 246 patients, confirming that levosimendan significantly reduces mortality in patients with sepsis and septic shock, compared to dobutamine treatment84

In a retrospective observational study, which included 10,700 patients undergoing cardiac surgery, milrinone versus dobutamine was compared, to assess mortality from all causes, finding that the intraoperative use of milrinone in cardiac surgery may be associated with an increase in mortality compared to Dobutamine use.85

No specific studies on vasoactive support of the septic patient in cardiac surgery were found in this search and its use is extrapolated from the general recommendations of the patient in septic shock,1 and in Japan the vasoactive score has been implemented- inotropic (VIS), which is a scale that shows the amount of vasoactive and inotropic support Recently, it was suggested that VIS after cardiac surgery predicts morbidity and mortality in pediatric patients, which is why a cohort study was conducted Retrospective of 129 adult patients of cardiac surgery concluding that the amount of cardiovascular support at the end of cardiac surgery can predict morbidity and mortality in adults, this scale being a prognostic tool Large studies are required to assess the real utility and its implementation widespread.86

Beta blockers

There is no available evidence on the use of beta blockers in the context of septic patients after cardiac surgery, the results of other critical care settings suggest that this option deserves research in future studies, in the environment of cardiovascular surgery13.

Adjuvant therapies

Extracorporeal blood purification therapies have been proposed as a strategy to regulate the general inflammatory response in sepsis. Small experimental studies have shown that wide reduction of inflammatory cytokines through adsorption can improve the outcome.87 In 2014, a multicenter randomized clinical trial was published, which included 192 patients, with discouraging results in terms of mortality reduction or improvement of other parameters.88 The above could be due to the fact that the release of cytokines is part of the host's response to maintain homeostasis and the overall reduction of cytokines could be harmful.

Endotoxins, on the other hand, play a crucial role in the pathophysiology of sepsis and the progression to dysfunction of multiple organs. To this extent, the use of hemoperfusion therapy with polymyxin B filters for the elimination of endotoxin has shown that it could improve renal and cardiovascular function and overall survival.89 A study of 65 patients with severe sepsis after cardiac surgery showed that the use of hemoperfusion with polymyxin B was associated with an improvement in hemodynamic parameters and a reduction in mortality at 28 days, which was reported as 42% in the study group, compared with 65% in the control group.90 Additionally, a retrospective study published in 2015 in 52 patients with septic shock refractory to treatment with high dose vasopressors showed a marked improvement in hemodynamic parameters, organ function and mortality, suggesting an important role as rescue therapy in patients. with refractory septic shock.89

The use of corticosteroids in septic patients in cardiac surgery is extrapolated from the recommendations of the septic patient of the general population.91 A systematic review and meta-analysis where 56 Randomized clinical trials (RCTs) were included, with a total of 16,013 patients found that mortality was not significantly different between the steroid group and the placebo group, myocardial injury was more frequent in the steroid group and the atrial fibrillation of new onset was lower in this group92

Progress has been made in the study of other adjuvant therapies proper in septic patients, such as hydrocortisone in combination with vitamin C, thiamine, however large trials are required to give a strong recommendation in this patient population93

As previously mentioned, it has been shown that the increase in blood glucose levels and variability are directly associated with a poor outcome, being called as an independent factor of mortality and development of deep sternal wound infection, and in this measure strategies have been implemented. Insulin infusion management both intra and postoperatively for cardiac surgery.13

The empirical antibiotic management in patients with suspected sepsis in the postoperative period of cardiac surgery will depend to a large extent on the suspected infectious focus, since it is always controlled if necessary with surgical reintervention, with a broad-spectrum empirical treatment that provides coverage to patients. responsible germs in greater proportion and directing the therapy according to the report of the sepsis cultures and breads according to the institutional availability.13

Monitoring

Hemodynamic monitoring is an important aspect in cardiac surgery, both in the perioperative and postoperative. The use of the appropriate technique depends on the patient's clinical scenario. The pulmonary artery catheter is a standard tool that can be used to assess trends and direct therapy for both liquids and vasoactive agents, although its use has been declining over the years. There are other techniques, such as a pulse contour analysis or minimally invasive monitoring devices, which can be validated at a particular stage. Echocardiography is an important tool available to the patient's bedside to assess additional overload, contractility and complications in the patient in cardiac surgery susceptible to intervention such as pneumothorax or cardiac tamponade and has been revolutionizing the evaluation of the patient in ICU94

Infection prevention in cardiac surgery

Preventive strategies should include both antibiotic prophylaxis, according to institutional protocols, and clinical processes that limit the factors that cause the release of endotoxins and packages (Bundles) for the prevention of infections in the intensive care unit (ICU).42

Antibiotic surgical prophylaxis before cardiac surgery is recommended to reduce the incidence of serious infections. First and second generation cephalosporins are the best studied antimicrobial agents for the prevention of ISO in cardiovascular procedures.95 The use of second-generation cephalosporins was associated with a 30% reduction in the development of severe gram-positive and gram-negative infection compared to prophylaxis with first-generation cephalosporins.96 The results of a recent meta-analysis that included a total of 14 studies, with high heterogeneity index (I2 63%) showed a significant reduction in the risk of infection of the sternal wound after implantation of gentamicin-collagen sponges.97 Powerful studies are required to confirm the benefit of additional local intervention in certain patient populations.

The 2017 guidelines 12have defined antibiotic prophylaxis in cardiac surgery by administering fixed doses instead of weight-based doses, which should not routinely exceed the usual dose in adults. In patients with obesity, although dosage adjustments are not well defined, it is accepted that, for patients weighing more than 120kg, the dose of cephalosporin should be doubled.4 For patients with renal impairment, the dose should be adjusted according to the creatinine clearance. It is recommended to repeat the intraoperative dose to ensure adequate serum and tissue concentrations if the duration of the procedure exceeds 2 half-lives of the antibiotic agent or when there is an excessive loss of intraoperative blood.12 The optimal duration of antimicrobial prophylaxis after cardiothoracic procedures is controversial,4 based on the evidence, a 2008 randomized trial, which included 838 patients, compared the administration of a single dose versus a regimen of 24-h multiple dose Cefazolin, reporting higher rates of ISO in patients receiving the single dose regimen98

A 2011 meta-analysis that included 12 randomized clinical trials (RCTs), with a total of 7893 patients showed that the administration of antibiotic prophylaxis>24h versus<24h, significantly reduced the risk of infection of the operative site by 38% (95% CI 13–69%, p=0.002) and the risk of deep sternal wound infections in 68% (95% CI: 12–153%, p=0.01)99

Proper prophylaxis should be administered at least 60min before the incision, if the regimen is vancomycin, it is 120min before starting surgery,4 and the need to repeat a dose will depend on the duration of the procedure, the amount of bleeding Regarding prophylaxis time, regimens of up to 48h have been administered and several reports have indicated that prophylaxis for a duration of one to four days failed to show any reduction in ISO compared to 24-h prophylaxis or single dose prophylaxis during the operation and if they are related to antibiotic resistance and complications from C. difficile. That said, it is not beneficial to extend the duration of antimicrobial prophylaxis until permanent lines, drains and catheters are removed,4 and based on current evidence, the optimal prophylaxis time Antibiotic in cardiac surgery in adults is 24h and should not exceed 48h.12 It is still unclear whether intermittent or continuous administration of antibiotics is preferred, although there is evidence to suggest that continuous infusion may reduce postoperative infectious complications, taking into account the pharmacokinetics of the drug and changes in the pharmacodynamics of the critical patient.100

There is no evidence to support the routine use of vancomycin for antimicrobial prophylaxis, even in institutions where the prevalence of S. aureus resistant to Meticillin (MRSA) is high, however, vancomycin prophylaxis is indicated for patients known to be colonized with MRSA and/or patients at high risk of MRSA infection. Due to the increase in the number of Methicillin-resistant Staphylococcus aureus infections in patients undergoing cardiac surgery, the importance of eradicating intranasal colonization by Staphylococcus aureus 101is highlighted. A randomized clinical trial (RCT) published in Lancet in 2016, concluded that the administration of intranasal mupirocin twice daily for 4 days before cardiac surgery, significantly reduces operative site infections (ISO) in patients with colonization by Staphylococcus aureus.102 However, for patients in whom colonization status is unknown, diagnostic tests prior to cardiac surgery should be considered to allow for the appropriate preoperative duration of mupirocin eradication treatment.12

For patients with beta-lactam allergy, vancomycin or clindamycin are acceptable alternatives for gram-positive coverage. An additional agent for gram-negative pathogens (such as an aminoglycoside, aztreonam or rarely a fluoroquinolone) may be needed in the context of ISO risk due to these organisms.12

Antibiotic prophylaxis guidelines are similarly assumed for procedures such as implantation of new devices, replacement of the permanent pacemaker generator, defibrillator implantation, flexible cardioverters and cardiac resynchronization devices.12

Rapid extubation strategy protocols have been implemented in the operating room to reduce infectious and cardiovascular complications in the postoperative period. A 2019 Colombian study of 396 patients randomized 207 patients to the ultra-fast extubation strategy arm (UFTE) versus an arm of 189 patients who were conventionally extubated. The results found that ultra-rapid extubation decreases cardiovascular morbidity and vasopressor requirement, without reducing the length of stay in the ICU, hospital stay or mortality. This study has some limitations such as the heterogeneity of its study population, however, its promising result.103 Larger studies are required to assess the impact of early extubation in relation to the development of sepsis in patients undergoing cardiac surgery.

Conclusions

Sepsis after cardiac surgery is a rare event, considering that there are no different definitions for this population group and the difficulties in diagnosis since the manifestations of septic shock can be confused with the normal course of the postoperative period or with other complications more frequently associated with extracorporeal circulation. Cardiac surgery patients form a very heterogeneous and challenging patient population. Your risk of developing postoperative sepsis depends on many different factors and should be assessed individually. Patients undergoing cardiac surgery are increasingly older and have multiple comorbidities. Cardiac patients are already compromised and obtaining hemodynamic stability and adequate tissue perfusion during the course of sepsis presents a particular challenge.

Different prevention strategies for postoperative infections are recognized in clinical practice guidelines, including appropriate antibiotic prophylaxis, selective decontamination of the digestive tract, maintenance of blood glucose levels, restrictive transfusion and weaning. Early mechanical ventilation. The treatment is directed to the infectious focus that is suspected and should be adjusted to the microorganism isolated in the cultures, taking into account the therapeutic implementation early as indicated in the sepsis and septic shock guidelines for the general population, namely, aggressive resuscitation, adequate antibiotic treatment, source control and organ support. The development of sepsis and septic shock in this population worsens the results in terms of mortality, morbidity, hospital stay and costs of medical care.

Author contributions

DAR and DRE formulated the research questions, designed the article, developed the preliminary search strategy, and drafted the manuscript. MAF refined the search strategy, conducted the quality assessment and performed the full translation of the manuscript. All authors critically reviewed the manuscript for important intellectual content. All authors have read and approved the final version of the manuscript.

Financing

The article did not receive financing.

Conflict of interest

All authors report no potential conflicts.

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