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Acta Colomb Cuid Intensivo. 2020;xxx(xx):xxx---xxx

Acta Colombiana de
Cuidado Intensivo
www.elsevier.es/acci

REVIEW ARTICLE

Sepsis after cardiac surgery: The clinical challenge.

Review article
Diana Ávila Reyes a,∗ , David Ricardo Echeverry Piedrahita b,c , Mateo Aguirre Flórez d

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

Received 12 February 2020; accepted 12 May 2020

KEYWORDS Abstract
Cardiovascular Introduction: Sepsis continues to be a clinical condition with an ostensibly high mortality
infections; despite efforts in early detection and therapeutic interventions, and its incidence in the post-
Cardiac surgery surgical cardiac surgery patient is relatively low. However, when sepsis or septic shock develops
procedures; in this scenario, it has a negative impact on the results. Regardless of the procedure performed,
Sepsis; the success of the outcomes depends on the optimal postoperative care in the Intensive Care
Shock; Unit, in order to improve the results and to have an effect on the morbidity and mortality.
Critical care 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 Sci-
ence/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.
© 2020 Asociación Colombiana de Medicina Crı́tica y Cuidado lntensivo. Published by Elsevier
España, S.L.U. All rights reserved.

∗ Corresponding author.
E-mail address: diana.avila@utp.edu.co (D. Ávila Reyes).

https://doi.org/10.1016/j.acci.2020.05.001
0122-7262/© 2020 Asociación Colombiana de Medicina Crı́tica y Cuidado lntensivo. Published by Elsevier España, S.L.U. All rights reserved.

Please cite this article in press as: Ávila Reyes D, et al. Sepsis after cardiac surgery: The clinical challenge. Review article.
Acta Colomb Cuid Intensivo. 2020. https://doi.org/10.1016/j.acci.2020.05.001
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2 D. Ávila Reyes et al.

PALABRAS CLAVE Sepsis en posquirúrgico cardiovascular: un reto clínico. Artículo de revisión

Infecciones
Resumen
cardiovasculares;
Introducción: La sepsis continúa siendo una condición clínica con una mortalidad ostensible-
Procedimientos
mente alta a pesar de los esfuerzos en la detección temprana y las intervenciones terapéuticas,
cirugía cardiaca;
y su incidencia en el paciente posquirúrgico de cirugía cardiaca es relativamente baja, sin
Sepsis;
embargo, cuando se desarrolla sepsis o choque séptico en este escenario, tiene un impacto
Choque;
negativo en los resultados. Independientemente del procedimiento realizado, el éxito de los
Cuidado crítico
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 car-
diovascular, 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 man-
ifestaciones 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.
© 2020 Asociación Colombiana de Medicina Crı́tica y Cuidado lntensivo. Publicado por Elsevier
España, S.L.U. Todos los derechos reservados.

Introduction difficile colitis and to a lesser extent provide urinary tract

Sepsis continues to be a clinical condition with ostensibly
high mortality despite efforts in early detection and thera-
peutic interventions,1 and its incidence in the post-surgical
cardiac surgery patient is relatively low, however, when Sep-
sis 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 surgi-
cal 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 infec-
tion (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 medi-
astinitis 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 postoper-
ative period are pneumonia, bloodstream infections, C.
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 require-
ment, ICU stay and hospital stay.9,10 Given 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 compli-
cation 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 car-
diac 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 post-
operative 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 spe-
cialist 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

Please cite this article in press as: Ávila Reyes D, et al. Sepsis after cardiac surgery: The clinical challenge. Review article.
Acta Colomb Cuid Intensivo. 2020. https://doi.org/10.1016/j.acci.2020.05.001
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Sepsis after cardiac surgery
to improve the results and obtain a positive impact in rela-
tion to reducing morbidity and mortality.16,17
In this review, the presentation of sepsis in post-surgical
patients of cardiac surgery, its pathophysiology, the diag-
nostic 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 22,23
or low cardiac output,24 conditions that could be present
in the patient undergoing cardiac surgery without the pres-
ence 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 interac-
tion between several molecular pathways, pro-inflammatory
responses, cytokine release, activation of the coagula-
tion cascade, complement system, and cellular components
of inflammation.25 Studies show that a percentage of
the population, when faced with the infectious pro-
cess, 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 recep-
tors (PRRs) on the surface of host immune cells recognize
pathogen-associated molecular patterns (PAMPs), such as
lipopolysaccharide (LPS) and associated molecular pat-
terns with danger (DAMPs), which are released in response
to inflammatory stress, triggered by surgical trauma or
cardiopulmonary bypass 27 Toll-like receptors (TLR) play a
central role in the inflammatory response since they con-
trol 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
Please cite this article in press as: Ávila Reyes D, et al. Sepsis after cardiac surgery: The clinical challenge. Review article.
Acta Colomb Cuid Intensivo. 2020. https://doi.org/10.1016/j.acci.2020.05.001
3
(CID); recognized factor as an independent predictor of
organic failure and mortality in the cardiovascular surgery
patient scenario 29 On the other hand, in patients during car-
diac surgery, the complement system is activated by several
mechanisms and its activation is involved in the inflamma-
tory response Previously, it was mentioned that the release
of endotoxins activates the complement through the alter-
nate 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 hypoper-
fusion 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 physiol-
ogy of the organism have been established from the moment
of the arrest related to multiple factors that directly influ-
ence 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 cardiopul-
monary 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 36 During 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 proce-
dures. Gram-negative microorganisms such as Enterobacte-
riaceae 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 Staphylo-
coccus aureus and Gram-negative bacteria infections are
associated with a higher mortality than patients with infec-
tions 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
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4 D. Ávila Reyes et al.
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 car-
diac 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 medi-
astinitis, pericarditis and myocarditis, have a relatively low
incidence, calculated in 0.25---5% of patients undergoing car-
diac 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, pro-
longed time of antibiotic therapy, hospital readmissions and
increased morbidity and mortality.43,44 Infections significan-
tly 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 48 h 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 pub-
lished in 2015, it was concluded that, within NAV prevention
strategies, the implementation of selective oral or diges-
tive 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 eval-
uate the efficacy of selective digestive decontamination,
without parenteral antibiotics for the prevention of pneumo-
nia 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 imple-
mentation of this measure.
The ISO correspond to sterile infections and mediastinitis
that significantly increase costs, days of care, mortal-
ity and correspond to a quality measurement factor in
medical care.46 Risk factors for ISO after cardiac proce-
dures include pre-existing peripheral chronic or vascular
Please cite this article in press as: Ávila Reyes D, et al. Sepsis after cardiac surgery: The clinical challenge. Review article.
Acta Colomb Cuid Intensivo. 2020. https://doi.org/10.1016/j.acci.2020.05.001
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 50 and 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 51,52 Due 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, com-
bined 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 pro-
cedures. In patients with CABG, bilateral removal of the
internal thoracic artery, the duration of the procedure that
exceeded 300 min, diabetes, obesity, chronic obstructive
pulmonary disease and female sex were independent pre-
dictors 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 infec-
tions and sepsis in cardiac surgery is the administration of
blood products.55 Restrictive transfusion strategies with a
defined threshold between 8 g/L and 10 g/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 prophy-
laxis 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 mak-
ing. 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 recogni-
tion 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 48 h and are
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Sepsis after cardiac surgery
negative even in the 30% of cases.1 In post-surgical cardiac
surgery patients, cultures may be altered and falsely nega-
tive 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 hav-
ing 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, vir-
ulence 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 sur-
gical 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 sep-
sis, 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 expres-
sion 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 pub-
lished in 2014,63 which included 151 patients, 32% of whom
were post-surgical cardiovascular surgery, it was found that
persistently elevated levels above >100 mg/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 differ-
ential 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 prospec-
tive study of 97 patients 64 postoperatively of cardiovascular
surgery, a serum PCT concentration > 10 ng/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 Procal-
citonin (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
Please cite this article in press as: Ávila Reyes D, et al. Sepsis after cardiac surgery: The clinical challenge. Review article.
Acta Colomb Cuid Intensivo. 2020. https://doi.org/10.1016/j.acci.2020.05.001
5
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 pre-
dict 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 under-
going 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 per-
ceived as a control of activated monocyte-macrophages in
response to pathogens. It represents a biomarker of the ini-
tial 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 preop-
erative 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 men-
tions 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 postop-
erative 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 predic-
tive 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 dif-
ferent cells and tissues, such as leukocytes, adipocytes and
endothelium. This cytokine is a reliable biomarker of cardiac
dysfunction, occurrence of atrial fibrillation, cardiac myx-
oma 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 periopera-
tive complications. It also predicts postoperative cardiac
function and complications, such as infection, atrial fib-
rillation, cardiac dysfunction and recurrence or myxoma
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6 D. Ávila Reyes et al.
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 under-
going 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 mor-
tality and morbidity.72 Another study of 122 cardiac surgery
patients evaluated the ratio of concentrations. of procalci-
tonin 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 73 Larger 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 postop-
erative 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 treat-
ment 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 ele-
ments of care consist of seven objectives: four will be
completed within the first 3 h and three will be completed
within 6 h. Septic patients should be treated with broad-
spectrum antibiotics within the first hour after diagnosis.75,76
Ideally, the initial antibiotic treatment should be adminis-
tered 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 car-
diovascular disorders.79 This measure requires monitoring
volumetric management using dynamic measures of preload
assessment to determine which patients are responders
Please cite this article in press as: Ávila Reyes D, et al. Sepsis after cardiac surgery: The clinical challenge. Review article.
Acta Colomb Cuid Intensivo. 2020. https://doi.org/10.1016/j.acci.2020.05.001
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 sus-
ceptible to this complication or they may already have
preoperative myocardial insufficiency.2
Norepinephrine continues to feel the first line of mana-
gement 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 arrhyth-
mias 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 oxy-
gen 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, com-
pared to dobutamine or the placebo.83 Other studies have
demonstrated a hemodynamic improvement in patients with
sepsis who received levosimendan, in addition, the cardio-
protective 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 levosimen-
dan 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 ver-
sus 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 mor-
tality 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 vasoac-
tive score has been implemented- inotropic (VIS), which is a
scale that shows the amount of vasoactive and inotropic sup-
port 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
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ACCI-258; No. of Pages 12 ARTICLE IN PRESS
Sepsis after cardiac surgery
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 pro-
posed 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 multicen-
ter randomized clinical trial was published, which included
192 patients, with discouraging results in terms of mortal-
ity 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 hemoperfu-
sion therapy with polymyxin B filters for the elimination of
endotoxin has shown that it could improve renal and car-
diovascular 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 asso-
ciated 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 con-
trol 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 tri-
als (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 fibril-
lation 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 indepen-
dent 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 infec-
tious focus, since it is always controlled if necessary with
surgical reintervention, with a broad-spectrum empirical
treatment that provides coverage to patients. responsi-
ble germs in greater proportion and directing the therapy
Please cite this article in press as: Ávila Reyes D, et al. Sepsis after cardiac surgery: The clinical challenge. Review article.
Acta Colomb Cuid Intensivo. 2020. https://doi.org/10.1016/j.acci.2020.05.001
7
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 stan-
dard 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 tech-
niques, such as a pulse contour analysis or minimally invasive
monitoring devices, which can be validated at a particu-
lar stage. Echocardiography is an important tool available
to the patient’s bedside to assess additional overload, con-
tractility 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 pro-
phylaxis, 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 12 have defined antibiotic prophy-
laxis 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 120 kg, 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 exces-
sive 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 administra-
tion of a single dose versus a regimen of 24-h multiple dose
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ACCI-258; No. of Pages 12 ARTICLE IN PRESS
8 D. Ávila Reyes et al.
Cefazolin, reporting higher rates of ISO in patients receiving
the single dose regimen98
A 2011 meta-analysis that included 12 randomized clin-
ical trials (RCTs), with a total of 7893 patients showed
that the administration of antibiotic prophylaxis > 24 h ver-
sus < 24 h, 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 60 min
before the incision, if the regimen is vancomycin, it is
120 min 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 48 h 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 pro-
phylaxis 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 24 h and should not exceed 48 h.12 It is
still unclear whether intermittent or continuous administra-
tion of antibiotics is preferred, although there is evidence to
suggest that continuous infusion may reduce postoperative
infectious complications, taking into account the pharma-
cokinetics 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 insti-
tutions 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 Staphylococ-
cus aureus infections in patients undergoing cardiac surgery,
the importance of eradicating intranasal colonization by
Staphylococcus aureus 101 is highlighted. A randomized clin-
ical 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 coloniza-
tion 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 fluoro-
quinolone) 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, replace-
ment of the permanent pacemaker generator, defibrillator
implantation, flexible cardioverters and cardiac resynchro-
nization devices.12
Rapid extubation strategy protocols have been imple-
mented in the operating room to reduce infectious and
Please cite this article in press as: Ávila Reyes D, et al. Sepsis after cardiac surgery: The clinical challenge. Review article.
Acta Colomb Cuid Intensivo. 2020. https://doi.org/10.1016/j.acci.2020.05.001
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 require-
ment, 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 develop-
ment 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 fre-
quently 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 infec-
tions are recognized in clinical practice guidelines, including
appropriate antibiotic prophylaxis, selective decontamina-
tion of the digestive tract, maintenance of blood glucose
levels, restrictive transfusion and weaning. Early mechani-
cal 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 popula-
tion, namely, aggressive resuscitation, adequate antibiotic
treatment, source control and organ support. The develop-
ment 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 strat-
egy, 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.
+Model
ACCI-258; No. of Pages 12 ARTICLE IN PRESS
Sepsis after cardiac surgery
Conflict of interest
All authors report no potential conflicts.
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