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OPINION Endocarditis in the intensive care unit: an update
Ines Lakbar a, Louis Delamarre a, Sharon Einav b and Marc Leone a
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Purpose of review
The incidence of infective endocarditis (IE) is increasing worldwide, resulting in a higher number of patients
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with IE being admitted to intensive care units (ICU). Nearly half of patients with IE develop a complication
during their clinical course. However, few well conducted studies or reviews are devoted to critically ill IE
patients. This review discusses the contemporary perioperative and intensive care literature.
Recent findings
IE epidemiology is changing towards elderly and frail patients. ICU patients are at risk of risk of
developing IE because they are often in a pro-inflammatory state and many also have several indwelling
catheters, which favors infection. Increased performance and recent advances in cardiac imaging allow for
easier diagnosis of EI, but the applicability of these techniques to ICU patients is still relatively limited. New
developments in antibiotic treatment and adjunctive therapies are explored further in this review.
Summary
The lack of evidence on ICU patients with IE highlights the critical importance of multidisciplinary decision-
making and the need for further research.
Keywords
critically ill patient, infective endocarditis, intensive care unit, outcomes
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therefore not specific to IE. Murmur is a classical delayed consultation and testing during the pan-
symptom, but auscultation can be difficult in ICU demic [30] have been shown to affect the diagnosis
patients, particularly in those requiring mechanical and management of IE, as well as other pathologies
ventilation or with tachycardia. Atypical clinical [30–36]. Hence physicians should maintain a high
presentations are therefore frequent in ICU patients. rate of suspicion in ICU patients regarding the pos-
Late diagnosis of IE, based on the occurrence of sibility of IE [30].
complications, is common. Furthermore, in many The cornerstone of diagnosis of IE remains visual-
cases, these complications are often the indication ization of the cardiac valves. Transthoracic echocar-
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for ICU admission in the first place [3 ]. These diography (TTE) is only moderately sensitive for
complications may be cardiovascular (22.6%), neu- detection of vegetations in both native (sensitivity:
&
rological (16.7%), renal (6.4%) or hematologic [3 ]. 60–70%) and prosthetic (sensitivity: 50%) valves [37].
About 1 in 10 patients with IE will also develop However, in most ICUs, this technique is immedi-
septic shock. Moreover, infection occurs in up to ately available and repeatable at the bedside by the
7.4% of prosthetic valves and 9% of implanted intensivist. Transesophageal echocardiography (TEE)
cardiac devices, but such infections often have mis- exhibits a much better performance for detection of
leading clinical and ultrasound presentations [25]. vegetations, with a sensitivity of 90–100% and 90%
Finally, the diagnosis of other diseases, sharing in native and prosthetic valves, respectively [37].
those nonspecific symptoms, can be falsely priori- The diagnostic criteria of IE have been modified
tized, as it has been the case during the coronavirus in 2015, through the introduction of the modified
disease 2019 (COVID-19) [26–29]. Furthermore, Duke criteria in the North American guidelines [38]
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FIGURE 2. The common etiologies of infectious endocarditis according to the location of the involved valve [79].
and the European Society of Cardiology (ESC) cri- Some authors therefore propose to combine both
teria in the European guidelines [24]. techniques when prosthetic valve endocarditis is sus-
The 2015 ESC diagnostic criteria added three pected. The pharmacological reduction of heart rate
elements to the modified Duke criteria [39]. Two of that is recommended to ensure good-quality images
&
those three, suggested as major criteria, involved the may limit the use of cardiac CT in ICU patients [40 ].
use of advanced cardiac imaging techniques to detect This imaging tool should therefore probably be
cardiac lesions attributable to IE, whereas the detec- chosen only when performing TEE is not feasible.
tion of recent silent embolic events or infectious The comparative performances of TEE and cardiac
aneurysms by imaging is proposed as a new minor CT are presented in Table 1 and Fig. 3.
criterion. The new major criteria based on cardiac The second imaging technique recommended in
imaging techniques are the detection of paravalvular the ESC guidelines, 18F-FDG PET/CT, relies on 18F-
lesions by cardiac multislice computed tomography FDG uptake by white blood cells after an injection 1-h
(CT) and the detection of abnormal activity on pros- prior to imaging. 18F-FDG PET/CT has a sensitivity of
thetic valve by 18F-flurodeoxyglucose (FDG) positron 67–80%, specificity of 75%, positive predictive value
emission tomography/computed tomography (PET/ of 90% and negative predictive value of 40% for
&
CT) or radiolabelled leucocyte single-photo emission the diagnosis of prosthetic valve endocarditis [44 –
computed tomography (SPECT/CT). 46], and a sensitivity and specificity of 85% for the
Cardiac multislice CT is a high-resolution diagnosis of infection in implanted cardiac devices
(<1 mm) imaging technique of the heart after ECG- [47]. In native valve IE, known for inducing a smaller
white blood cell traffic [48], 18F-FDG PET/CT alone
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gated retrospective reconstruction [40 ,41]. Cardiac
CT has a performance almost similar to TEE for diag- showed a sensitivity within the range of 20–57% and
& & &
nosing IE [40 ,42 ]. However, cardiac CT better a specificity approximating 100% [49 ,50].
detects paravalvular abscesses and pseudo-aneur- The application of ESC criteria, including
ysms, whereas TEE seems to better detect vegetations those observed in 18F-FDG PET/CT, increased the
sized <10 mm and valvular perforations [41]. In sensitivity of modified Duke criteria for native valve
patients with prosthetic valves, the sensitivity of endocarditis from 63.5% to 70% without affecting its
specificity [49 ]. However, imaging with 18F-FDG
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CT and TEE seem similar, with a trend towards better
performance of cardiac CT for paravalvular abscesses, PET/CT requires fasting for 24 h, hemodynamic
vegetations and inflammatory infiltrations, whereas stability and sometimes heparin (50 UI/kg)
& & & &
TEE better detects paravalvular leakage [40 ,42 ,43 ]. to enhance glucose/FDG uptake [48,51,52 ].
Table 1. Summary of the morphological diagnosis tools in infective endocarditis, with considerations pertaining to their use in ICU
Performance in Availability/
Performance in prosthetic feasibility
Technique Indication native valves valves in ICU Contraindications Limitations in ICU References
TTE Suspected IE Se: 60--70% Se: 50% High None -Lower quality images in Pelletier-Galarneau [37]
ventilated patients
-Operator-dependent ac
curacy
TEE -Suspected IE Se: 90--100% Se: 90% High Esophageal surgery, -Requires sedation Pelletier-Galarneau
&
-Confirmed IE mediastinum - Requires fasting [37], Sifaoui [42 ],
&
-Assessment of radiotherapy, unstable - Requires experienced Koo [40 ],
&
valve damage cervical spine fracture, operator (cardiologist Michalowska [43 ]
and heart upper airway mass or intensivist)
function -More difficult to visualize
-Preoperative prosthetic valves due to
assessment metal artifacts
&
Cardiac multislice -Suspected IE Accuracy: 92.6% Se: 92%, Sp: 86% Scarce data Not specific Heart rate 75 bpm Koo [40 ], Khalique
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computerized -Confirmed IE available facilitates ECG-gated [41], Sifaoui [42 ],
&
tomography (CT) -Assessment of analysis Michalowska [43 ]
valve damage Can be difficult or poorly
and heart tolerated in ICU
function patients
-Preoperative
assessment
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18
F-FGD PET/CT -Suspected IE Se: 20--57% Se: 67--77% Low, scarce Not specific Requires 24 h fasting, Mahmood [46], Venet
Sp: 100% Sp: 75% data available hemodynamic stability, [45], Abikhzer [50],
&
PPV: 91% avoidance of Philip [44 ], Philip
&
NPV: 42% corticosteroids and [49 ], van Hulst
&
hyperglycemia. [52 ], Schenone [83]
Heparin may enhance
image quality, but
potentially deleterious
in ICU patients
Radiolabelled -Complementary NA NA Low to very low Not specific Similar to 18F-FGD PET/ NA
leucocyte after 18F-FGD CT limitations
SPECT/CT PET/CT Requires
radiopharmaceutical
preparation of
autologous leucocytes.
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18
F-FGD PET/CT, F18-flurodeoxyglucose positron emission tomography and computed tomography; CT, computerized tomography; Se, sensitivity; Sp, specificity; SPECT/CT, single-photo emission computerized
tomography; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.
507
Endocarditis in the intensive care unit: an update Lakbar et al.
Severe infections
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FIGURE 3. Comparison of the performance of transesophageal echocardiography and multislice cardiac computed
tomography for the diagnosis of infective endocarditis. CT, computerized tomography; Se, sensitivity; Sp, specificity; TEE,
transesophageal echocardiography.
Concurrent administration of corticosteroids and the than modified Duke criteria for the diagnosis of
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presence of hyperglycemia have been associated with prosthetic valve endocarditis [44 ]. The performance
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false negative results [52 ]. Despite these limitations of those criteria in the ICU setting in not described.
of 18F-FDG PET/CT in ICU patients, the use of this tool An increasing proportion of ICU physicians
in such patients has been described by a few teams, have expertise in point of care ultrasound practice.
with successful diagnosis of IE in several cases The question whether the availability of ultrasonog-
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[52 ,53]. Unfortunately, there is still very little data raphy-trained physicians in the ICU facilitates the
on the performance and feasibility of nuclear imaging diagnosis of IE remains unresolved in the existing
in ICU patients and no data on the performance of literature. Lau et al. [54] reported similar perform-
nuclear imaging specifically for diagnosis of IE in ICU ance of intensivist-led vs. cardiologists-led TEE in
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patients [52 ]. ICU patients if the intensivists were board certified
Radiolabelled leucocyte SPECT/CT requires a for ultrasound. The 2016 guidelines for the training
radiolabeling of autologous leucocytes that, once standards in ultrasound in the ICU graded the skills
re-injected, will accumulate in damaged heart tissue of endocarditis diagnosis as a basic skill, whereas TEE
in a time-dependent fashion [24]. The data regard- and prosthetic valve endocarditis diagnosis were
ing its use in critically ill IE patients is insufficient to graded as advanced skills [25].
draw any assessment of its pertinence and feasibility
at the time of this writing. The characteristics and
performance of those diagnosis tools are presented Microbiological innovations
in Table 1. Finally, the 2015 ESC criteria have been Microorganism detection and identification have
shown to be more sensitive but not more specific dramatically improved over the last years, especially
due to the improvements in 16S-ARN PCR and Next- American guidelines highlight that initiation of
Generation Sequencing (NGS). The impact of these antibiotic treatment is rarely urgent in cases of IE
techniques has been mostly described in cases of [38]. In patients with septic shock, urgent introduc-
suspected IE with negative blood cultures, where tion of empirical antibiotics is recommended, and
NGS or 16S-RNA sequencing were performed post- this recommendation should therefore also apply to
operatively on valvular tissue [55–59], without spe- patients with known or suspected IE and septic
&&
cific application in the ICU setting. shock [61 ]. Of note, preliminary observational
data suggested that ceftaroline and ceftobiprole
could be used when staphylococci and enterococci
MANAGEMENT
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Table 2. The antibiotic regimens suggested in International guidelines (adapted from reference [60])
American Heart Association European Society of Cardiology (ESC)
(AHA) guidelines, 2015 [38] guidelines, 2015 [24]
Antibiotic treatment should be selected by consensus within the ‘‘Endocarditis Team’’, a team of experts including infectious diseases specialists, microbiologists,
cardiologists and intensivists.
Long-term gentamicin, listed as an option in the guidelines, has been deliberately omitted from this table because the authors believe that long-term
aminoglycosides should be reserved for difficult-to-treat multidrug-resistant infections owing to the high risk of acute kidney injury and muscle weakness in critically
ill patients [80]. This consideration is backed by expert opinion that aminoglycosides could be avoided in 90% of cases [81].
a
Rifampicin is only indicated for prosthetic valve endocarditis and should only be introduced 5--7 days after the start of the pivotal antiinfective regime [60].
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antibiotic levels in critically ill patients [67,68], including surgical, anesthetic and ICU teams in a
&&
which can be applied to the context of IE [69]. recent comprehensive review [5 ].
Oral treatment should be regarded as a step- Specifically, after cerebral embolism, delaying
down treatment and should be reserved only for surgery has been recommended due to the risk of
patients who have cleared their bacteremia [70]. infarct extension, hemorrhagic transformation of
an ischemic infarct and expansion of an intracranial
hemorrhage. Such practice has also not been associ-
Complications ated with higher mortality rates [71]. However recent
Septic shock and sepsis should be managed as recom- data have also shown that early and late surgery have
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mended in the Surviving Sepsis Campaign guidelines, the same outcomes in terms of mortality [71,72],
with early optimal management combining fluid which raises ongoing questions regarding the optimal
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resuscitation, antibiotic treatment and surgical con- delay for surgery. As for the treatment of the acute
&&
trol of the source of infection if necessary [61 ]. Car- ischemic stroke itself, thrombectomy has been
diac output should be closely monitored as it may be reported but its safety is yet to be proven [73,74].
impaired indirectly by the septic cardiomyopathy
associated with septic shock or directly by valvular
insufficiency. Cardiovascular complications, includ- Future
ing cardiac arrest, cardiogenic shock, acute myocardial As shown in experimental studies, a complex inter-
infarction, acute heart failure and heart block were action between bacteria, coagulation and innate
reported in almost a quarter of patients with IE, regard- immunity is mandatory for valve infection. There-
less of their location of treatment in hospital (i.e. fore, experimental and clinical studies have thus far
&
general ward or ICU) [3 ]. In the ICU, acute heart aimed to target platelets and coagulation factors in
failure (from septic or cardiogenic shock) was reported order to inhibit vegetation growth and embolic
in more than half of the patients with IE [6]. events, using aspirin as prophylactic or adjunctive
The indications for urgent surgery in both Amer- treatment. Clinical findings have already yielded
ican and European international guidelines are conflicting results regarding the use of aspirin as
heart failure, along with uncontrolled infection prophylactic treatment for IE, in patients receiving
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(ongoing bacteriemia, local abscesses and fistulae) aspirin for long-term treatment [75 ]. In a mouse
and emboli prevention (in cases of recurrent emboli model of bacteremia, the use of ticagrelor enhanced
or large vegetations) (Table 3). However, there are platelet killing of S. aureus [76,77]. It has therefore
discrepancies between American and European been advocated that further studies should evaluate
experts regarding the timing of surgery. American ticagrelor for prophylactic treatment of IE in
experts recommend early surgery, while European patients with prosthetic valves or indwelling devi-
&
experts highlight the need to weigh the benefits of ces [75 ]. Experimental studies also reported
antibiotic completion before surgery against the risk improved outcomes in terms of vegetation size,
of an uncontrolled source of infection. This lack of bacterial load and inflammation reduction with
agreement in the guidelines highlights the paucity the use of dabigatran, a direct thrombin inhibitor
&
of evidence in the literature and has led anesthesi- [78 ]. However, such treatments in are challenging
ologists to advocate for multidisciplinary decisions, in ICU patients, as they were associated with a
&
major risk of bleeding [75 ].
Table 3. Indications for surgery in infective endocarditis Hyperbaric oxygen therapy could also be an
[24,38] adjunctive treatment worth exploring in patients
with IE. In experimental models of IE, hyperbaric
Indication for surgery Symptoms
oxygen therapy has been shown to enhance the
&
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