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Dental Abscess to Septic Shock – A Case Report and Literature Review

  • University of Maryland, School of Dentistry

Abstract and Figures

Sepsis is a leading cause of death in the United States, with a mortality rate in excess of 215,000 deaths per year. It may lead to septic shock - a complex pathophysiological process with microbial and host response events that progress to multisystem derangement. There is poor documentation of the relationship between dental infection and septic shock, with only a few case reports of septic shock secondary to dentoalveolar abscess. Presented is a review of sepsis/septic shock with a description of a 23-year-old male with signs and symptoms of necrotic pulp, acute apical abscess, and canine space infection that rapidly progressed to an altered mental state, hyperthermia, tachycardia, hypotension, acute respiratory failure, diarrhea, renal insufficiency, lactic acidosis, leukocytosis and hyperglycemia. Once septic shock develops, the mortality rate is nearly 50%. Early antimicrobial intervention is associated with surviving severe sepsis, making it critical for dentists to understand local factors leading to the crisis, and the signs and symptoms of the sepsis-septic shock continuum.
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Dental Abscess to Septic
Shock: A Case Report and
Literature Review
Sepsis is a leading cause of death in the United States, with a mortality rate in excess of
215,000 deaths per year. It may lead to septic shock, a complex pathophysiological process
with microbial and host response events that progress to multisystem derangement. There is
poor documentation of the relationship between dental infection and septic shock, with only a
few case reports of septic shock secondary to dentoalveolar abscess. Presented is a case of
sepsis/septic shock in a 23-year-old man with signs and symptoms of pulpal necrosis, acute
apical abscess, and canine space infection that rapidly progressed to an altered mental state,
hyperthermia, tachycardia, hypotension, acute respiratory failure, diarrhea, renal insufciency,
lactic acidosis, leukocytosis, and hyperglycemia. Once septic shock develops, the mortality
rate is nearly 50%. Early antimicrobial intervention is associated with surviving severe sepsis,
making it critical for dentists to understand local factors leading to the crisis and the signs and
symptoms of the sepsisseptic shock continuum. (J Endod 2021;47:663670.)
Bacteremia; dentoalveolar abscess; odontogenic infection; sepsis; septic shock
Sepsis is a serious, complicated medical condition with a high mortality rate. Sepsis and septic shock
are 2 entities occurring as a continuum, with sepsis leading to septic shock
. Sepsis was rst dened
in 1991 as a systemic inammatory response syndrome due to suspected infection with 2 or more
specied clinical criteria. Septic shock includes hypotension and organ dysfunction that persists
despite volume resuscitation, along with the systemic inammatory response syndrome criteria
Using these denitions, the Surviving Sepsis Campaign developed guidelines for a protocol-driven
model of care
. In 2016, the international Sepsis-3 Committee dened sepsis as a life-threatening
condition caused by a dysregulated host response to infection, resulting in organ dysfunction,
whereas septic shock is circulatory, cellular, and metabolic abnormalities in septic patients,
presenting as uid-refractory hypotension requiring vasopressor therapy with associated tissue
hypoperfusion (lactate .2mmol/L)
In the United States, the incidence of severe sepsis is estimated to be 300 cases per 10,000
, with over 30 million cases of sepsis/annum estimated worldwide
. More than 500,000
annual emergency department visits in the United States are related to sepsis
. In 2013, sepsis-related
illness was the most expensive reason for hospitalization, costing $23.7 billion
. One study reported the
mortality rate of sepsis as 33%35%
, whereas hospital deaths in patients with sepsis from 2
independent cohorts found mortality ranged between 34%56%
. With sepsis-related mortality
above 215,000 deaths per year, it is a leading cause of death in the United States
In 2013, New York state was the rst to implement regulations that require hospitals to follow
protocols for treating sepsis, which resulted in a greater decrease in sepsis mortality compared with
control states without regulations
. Illinois, New Jersey, and Indiana also have mandatory practices,
whereas other states have introduced bills into legislature as recently as 2020 or use voluntary
. In 2018, Maryland developed a public awareness campaign to help prevent sepsis
We report a case of an urgent care visit to a dental school clinic for treatment of an endodontic and
canine space infection that quickly escalated to a medical emergency and near-death experience for the
patient because of sepsis and septic shock.
This is a report of a healthy 23-
year-old male who presented
to the urgent care clinic of a
dental school for treatment of
an endodontic and canine
space infection. The patients
condition rapidly deteriorated
to a medical emergency and
near-death experience
because of sepsis and septic
shock. Signicant changes in
vital signs are not expected in
localized infections. Hence, all
vital signs should be routinely
checked while examining
infected dental patients.
From the *Endodontics Division,
Department of Advanced Oral Sciences
and Therapeutics, University of Maryland
School of Dentistry, Baltimore, Maryland;
Department of Endodontics,
Rutgers School of Dental Medicine,
Newark, New Jersey
Address requests for reprints to Dr
Patricia A. Tordik, Endodontics Division,
Department of Advanced Oral Sciences
and Therapeutics, University of Maryland
School of Dentistry, 650 W Baltimore
Street, Baltimore, MD 21201.
E-mail address:
0099-2399/$ - see front matter
Copyright © 2021 American Association
of Endodontists.
Saurabh Mannan, BDS, DMD,
MPH, MS,*Patricia A. Tordik,
DMD,*Frederico C. Martinho,
DDS, MSc, PhD,*Noah Chivian,
and Craig S. Hirschberg,
JOE Volume 47, Number 4, April 2021 Dental Abscess to Septic Shock 663
Day 1
0900 Hours
A 23-year-old man presented to the
predoctoral urgent care clinic with a chief
complaint of an ongoing toothache and
severe pain.His past medical history was
noncontributory with no known drug allergies;
his past dental history included caries in tooth
#7. The patient was taking acetaminophen. His
vital signs are provided in Table 1. A limited oral
examination revealed pulpal necrosis/acute
apical abscess in tooth #7. For pain
management, 1 cartridge of lidocaine with
1:100,000 epinephrine (34 mg lidocaine
hydrochloride/0.017 mg epinephrine) mesial
and distal to the infected area was
administered using a standard local inltration
1030 Hours
A dental student was assigned to initiate root
canal treatment of tooth #7 in the predoctoral
endodontics clinic later the same day. With
pain relief, the patient planned to hydrate and
eat a light meal before his appointment.
1415 Hours
The patient presented to the predoctoral
endodontics clinic. Despite having a toxic
appearance, he was alert; was oriented to
person, place, time, and situation; and was in
no respiratory distress. The attending faculty
made a cursory diagnosis of canine space
infection and immediately transferred care to
the on-call postgraduate endodontic resident.
1430 Hours
His past medical and dental history was
reviewed, medications were reconciled, and
no known drug allergies was noted. His vital
signs are presented in Table 1. The clinical/
radiographic data are provided in Table 2.A
periapical radiograph was provided by the
urgent care clinic (Fig. 1). The patient said he
felt cold and was given a blanket.
1440 Hours
Within 10 minutes of evaluation, intense
shivering ensued. The patient was lethargic
and hyperthermic. His tympanic temperature
and vital signs are presented in Table 1.
Emergency medical service (EMS) was
activated. Until the paramedics arrived, the
patient was semireclined, his airway was
maintained, respiration was supported with
100% oxygen, and ice packs were applied to
the forehead and axillae. The patient became
tachypneic, difcult to arouse, and lost
consciousness after EMS arrival. Because of
the suspected contribution of the dental
infection, the attending endodontist requested
the patient be transported to the university
hospital emergency department (ED), where
there is an oral and maxillofacial surgery
service, rather than to the city hospital on call.
The ED consented to accept the patient.
Tachycardia was refractory to 6 mg adenosine
provided en route to the ED. His vital signs are
recorded in Table 1. A review of his systems
are included in Table 3.
1810 Hours
The patient was sedated with propofol and
benzodiazepine and then intubated to protect
the airway. A full-body computed tomographic
scan was ordered because of the sudden
alteration in mental awareness. The differential
diagnosis included meningitis, encephalitis,
septic encephalopathy, toxin/ingestant, and
seizure/postictal. The immediate treatment
plan was for magnetic resonance imaging and
electroencephalography while awaiting the
results of urodynamic studies and lumbar
puncture. To manage possible infection, the
patient was given intravenous cefepime,
vancomycin, and metronidazole, which was
later changed to ceftriaxone, vancomycin,
metronidazole, and acyclovir. A lactated Ringer
solution bolus was administered for uid
2334 Hours
The patient had elevated troponin, lactate, and
creatinine values (Table 3). Primary cardiac
pathology was considered not likely,
transthoracic echocardiography was planned,
and the patient was admitted to the critical
care resuscitation unit.
Day 2
Approximately 8 hours after admission, the
working diagnosis included septic shock,
central nervous system failure or compromise,
metabolic crisis, acute respiratory failure, renal
insufciency, elevated liver enzymes,
leukocytosis, and fever. The transthoracic
echocardiographic nding was tachycardia
secondary to sepsis, volume depletion, and
fever. Heart rate decreased with volume
resuscitation, leading to the conclusion of
sinus tachycardia. Norepinephrine bitartrate
(Levophed; CIBA, Basel, Switzerland) was
administered to maintain a mean arterial
pressure .65 mm Hg based on the bedside
echocardiogram suggesting myocardial
dysfunction and euvolemia. Full ventilator
support continued until vast improvement
allowed for extubation. Findings of
reconstructed computed tomographic
images, taken with contrast to evaluate for
infection, were unremarkable (Table 4).
TABLE 1 - Vital Signs as Recorded in the Medical Record
Day Time BP Pulse (beats/min) HR R (Rate) R (Rhythm) R (Depth) SpO
(F) Temp (C)
(mm Hg) Arterial BP
1 0900 155/96*80 12 Regular Normal
1 1430 170/104*100*12 Regular Normal
1 1440 170/100*160*18*Increased Shallow 106*41.1*
1 1533 135/98*183*174*20*Increased Shallow 97*102.9*39.4*
1 1931 113/66 128*114*20*Increased Shallow 100 100*37.8*
2 0200 95/54*79 75 15 Regular Normal 100 98.6 37*67.67*114/53
BP, blood pressure; HR, heart rate; MAP, mean arterial pressure; R, respiration; SpO
, oxygen saturation.
*Values outside of the normal range.
TABLE 2 - Clinical and Radiographic Data Collection
Tooth Swelling
Lymphadenopathy upon
palpation ST Cold Hot EPT Percussion Palpation
radiolucency (mm)
CS, canine space; EPT, electric pulp test; N, none; NR, no response; NT, not tested; S, sensitive; ST, sinus tract; V, vestibular.
664 Mannan et al. JOE Volume 47, Number 4, April 2021
Day 3
The oral and maxillofacial surgery service
completed a head/neck examination. Extraoral
swelling with obliteration of the nasiolabial fold
and a broad, uctuant swelling in the vestibule
were noted. A diagnosis of acute apical
abscess/canine space infection associated
with tooth #7 was made. After inltrating with
lidocaine/epinephrine, a vestibular, horizontal
incision was made extending from tooth #6 to
tooth #8. Subperiosteal blunt dissection
produced purulent and sanguineous drainage.
Tissues were irrigated with a high volume of
0.9% normal saline, and a gauze pressure
dressing was placed.
Day 4
An improvement in fever, leukocytosis, and
hemodynamics was noted. The clinical course
of infection was improving.
Day 5
The patient was discharged to home with a
7-day course of amoxicillin/clavulanate
potassium 875 mg and 30 mL 0.12%
chlorhexidine gluconate oral rinse. He was
advised to follow up with the dental school,
where the nonsurgical root canal treatment
was completed by the same predoctoral
student, 3 months later (Fig. 2). The discharge
note stated the following: Because of likely
dental abscess, the patient was hypotensive
on presentation and showed signs of ischemic
end organ damage with lactic acidosis,
transaminitis, troponinemia, acute kidney injury
and altered mental status (AMS), requiring
Except when pathogens directly enter the
bloodstream, sepsis occurs in 2 stages:
preseptic and septic. With direct
contamination, the preseptic stage is absent
Previously, it was believed the immune system
maladaptive response played the predominant
role in presepsis
. New information
suggests pathogens are also involved
Preseptic and Septic Bacterial Role
The primary sources for bacteria entering the
bloodstream include local infection, lungs,
lymphatics, venous system, or intestines. Only
erythrocytes clear bacteria from the
. The erythrocyte membrane is
triboelectrically charged to attract bacteria.
Once xed to the membrane, oxyhemoglobin
is released, killing most bacteria
bacterium survives oxidation, it can be trapped
in the concave pocket of an erythrocyte. Once
trapped, it is either oxidized and released into
FIGURE 1 – The periapical radiograph provided by the urgent care clinic.
TABLE 3 - A Review of the Systems and Pertinent Values from the Comprehensive Metabolic Panel
Normal ndings Abnormal ndings
General Febrile, altered mental status:
nonverbal, agitated, incoherent
Skin Diaphoretic
Head and neck No traumatic head injury or cervical
Pulmonary/chest No stridor or wheezes Tachypenia
Cardiovascular Regular rhythm, normal heart
sounds, and intact distal pulses;
no gallop; no friction rub; no
murmur heard
Sinus tachycardia, bedside
echocardiogram grossly
depressed with left ventricular
ejection fraction 525%35%
Gastrointestinal Normal bowel sounds, no
distention, no mass, no
tenderness, no rebound, no
Vomiting, diarrhea
Urinary UDS ordered
Genital All
Vascular All
Musculoskeletal All
Neurologic LP and EEG planned
Hematologic Comprehensive metabolic panel
Endocrine All Thyroid-stimulating hormone and
free thyroxine test planned
Psychiatric Indeterminate signs/symptoms due to altered mental state
Normal range Measured value
Creatinine 0.61.2 mg/dL 1.42 mg/dL*
Lactate 0.51.0 mmol/L 3.4 mmol/L*
Troponin 0.00.04 ng/mL 0.61 ng/mL*
EEG, electroencephalography; LP, lumbar puncture; UDS, urodynamic study.
*Elevated values.
JOE Volume 47, Number 4, April 2021 Dental Abscess to Septic Shock 665
plasma for digestion in the reticuloendothelial
system, released, and removed by the liver and
spleen or uses exotoxin to decompose the
erythrocyte membrane and enter the cell
Inside an erythrocyte, a bacterium is protected
from immune complexes and exogenous
antibacterial agents. Using hemoglobin, it can
multiply and rupture the membrane, releasing
new bacteria into plasma. This is a critical step
in developing sepsis
Motile and nonmotile bacteria resistant
to host immunity proliferate in tissue and enter
. Immunity-resistant features
include superoxide dismutase, catalase, and
gonyautoxin production. These enzymes
convert harmful superoxide to nontoxic water
and oxygen
. Likewise, a capsule, slime layer,
and biolm protect against phagocytosis, lytic
enzymes, immune complexes, reactive oxygen
species, and erythrocyte attachment
Sepsis-causing bacteria must also express a
large quantity/variety of virulence factors and
coordinate individual gene transcription to
maximize virulence potential
Gram-positive bacteria effectively
invade host tissue
and initiate sepsis via
exotoxins and the exposed cell wall
, whereas gram-negative
bacteria trigger sepsis through
lipopolysaccharide endotoxins
. Most sepsis
involves facultative anaerobic bacteria
, but
nonfacultative anaerobes also contribute.
Meanwhile, the bacterial etiology of
endodontic infection is well-documented
Endodontic infections contain both gram-
negative and gram-positive facultative and
obligate anaerobes, with the prevalent phyla
identied as Proteobacteria, Firmicutes,
Bacteroidetes, Fusobacteria, and
.Prevotella and
Porphyromonas spp. are associated with
symptomatic infected teeth and are thought to
play an essential role in severe infections
unknown how many cases of sepsis/septic
shock are the result of dental infections.
When erythrocytes are destroyed by
bacteria, inammation anemia occurs
. With
no erythrocytes to deliver oxygen to organs,
cell hypoxia results. The kidneys and liver
detect reduced blood oxygen levels and
secrete erythropoietin to stimulate bone
marrow erythropoiesis. This slightly increases
the blood oxygen transport capacity. Bacterial
attachment to erythrocytes causes premature
oxygen release, platelet activation, and
disseminated intravascular coagulation
which provides nutrients for bacterial
. Oxidative hormone inactivation
leads to muscle wasting and impaired
wound healing, whereas insulinlike growth
factor inactivation leads to hyperglycemia
Lower blood oxidation also affects the
TABLE 4 - Findings of Reconstructed Coronal and Sagittal Computed Tomographic Scans
Airway Bowel
Free air/
uid Heart/lungs Intracranial
lesions Osseous
Other organs/
Soft tissue
planes Thyroid Vasculature
Head and
Patent None Visible lung
apices: clear
Normal Normal Normal Paranasal sinuses,
mastoid air cells:
all well aerated
Normal Normal Intact
Chest and
Patent, no
Normal, no
evidence of
of ileum
None No pericardial
or pleural
vessels: normal
Lungs: clear; no
focal consolidation
atelectasis, nodules,
or masses
hill, and axilla
Normal Kidney enhancement
and excretion: normal
Liver, gallbladder,
pancreas, spleen,
adrenal glands: normal
Pelvis None Normal None Urinary bladder collapsed
with Foley catheter in place
666 Mannan et al. JOE Volume 47, Number 4, April 2021
hypothalamic-pituitary-thyroid axis, causing
adrenal and vasopressin insufciency and
thyroid hormone inadequacy. Vasopressin
oxidation along with low levels of angiotensin II
and angiotensin-converting enzyme contribute
to systemic vasodilation
. Resultant albumin
oxidation leads to hypoalbuminemia, which is
identied as an independent predictor of
sepsis mortality
. Lastly, inactivation of
immunoglobulins alters immunoreactivity
Preseptic and Septic Host Role
Prolonged overexpression of chemical
mediators required to recruit immune effector
cells evoke harmful biological effects
. Often
referred to as cytokine cascade/dysfunction, it
involves all cell types including antigen-
presenting cells, neutrophils, macrophages,
and lymphocytes. Once the cascade initiates
events, hypoxia and cellular hypoperfusion
lead to transitory organ failure
. Profound
oxidative cellular stress results in
catecholamine depletion, hormonal alterations,
vascular dysfunction, neural dysregulation,
and disruptions to immune/metabolic
activities. If the patient is not well managed,
health rapidly deteriorates. Symptoms include
cardiovascular depression, delirium, acute
respiratory distress syndrome, acute renal
failure, and hepatic dysfunction
. A nonlinear,
exponential relationship between cellular injury
and organ failure leads to a high level of
The effect of septic shock on the
cardiovascular system can be divided into 3
major events: vasodilation, maldistribution of
blood ow, and cardiovascular depression
Hypotension despite adequate uid
resuscitation reects the end of progressive
. Myocardial depressant factors
tumor necrosis factor alpha and interleukin 1
beta participate in cardiovascular
. These factors produce
abnormal amounts of nitric oxide and cyclic
guanosine monophosphate. Excessive nitric
oxide leads to decreased vascular resistance,
resulting in maldistribution of blood ow
also interacts with superoxide to form
peroxynitrite, which directly injures intracellular
. Mitochondrial injury limits the
ability of the cytochrome system to generate
adenosine triphosphate, leading to myocardial
depression. Excessive acetylcholine secretion
also leads to myocardial depression, but it can
inhibit tumor necrosis factor alpha expression,
improving survival
High concentrations of circulating
catecholamines produced in the early stages
of septic shock enhance the inammatory
response. Continuous elevated levels result in
depletion, perhaps because of apoptosis of
adrenal medullary cells
. Once depleted, the
patient is predisposed to peripheral
vasodilation, compromised myocardial
contractility, and myocardial depression
Hypotension, hypoperfusion, and organ
dysfunction follow. The concomitant abnormal
adrenergic modulation of heart/vessels during
septic shock indicates that adrenergic
regulation impairment contributes to
cardiocirculatory failure
Signs and Symptoms of Septic
Sequential (Sepsis-Related) Organ Function
Assessment (SOFA) scoring is an objective
method to determine dysfunction based on
oxygen levels, platelet count, Glasgow Coma
Scale (GCS) score, bilirubin level, creatinine
level, and mean arterial pressure
. Quick SOFA
(qSOFA) is simpler and predicts death risk
One point each is awarded for AMS (GCS
,15), respiratory rate 22 breaths/min, and
systolic blood pressure (BP) 100 mm Hg.
Patients with qSOFA scores of 23 are
associated with a 3- to 14-fold increase in
hospital mortality and should be further
assessed with blood testing, including serum
lactate, and full SOFA scoring
. When our
patient suffered from AMS and tachypnea, he
had a qSOFA score of 2.
Our patient presented with serious,
general signs of sepsis including all
components of a toxic appearance
. This
included an ill presentation, shivers/chills,
lethargy, diaphoresis, rapid pulse, and fever of
102107F. Upon arrival to the ED, our
patient was suffering from acute respiratory
Questioning an infected dental patient
can reveal if he or she is eating or sufciently
hydrated. Dentists should recognize the signs
and symptoms of dehydration, including a
drawn facial appearance, dry mucous
membranes, fever, loss of skin turgor, oliguria,
postural hypotension, serum electrolyte
changes, thirst, and weakness
. Our patient
was experiencing at least 6 of these signs and
FIGURE 2 – The immediate postobturation periapical radiograph. The nonsurgical root canal treatment was completed
by the predoctoral dental student.
JOE Volume 47, Number 4, April 2021 Dental Abscess to Septic Shock 667
Another symptom of sepsis is central
nervous system changes. Although our patient
was initially alert and oriented, his best eye,
verbal, and motor responses diminished over a
short period of time. Within 30 minutes, his
GCS score was 15, then 11, and then
unresponsive. A declining or waxing and
waningGCS is concerning, and the airway
should be reassessed for intervention
. Our
patient was intubated upon arrival in the ED.
Our patient had elevated creatinine
(1.42 mg/dL), lactate (3.4 mmol/L), and
troponin (0.61 ng/mL) values. Elevated
creatinine indicates kidney disease, shock,
dehydration, or congestive heart failure
. The
high lactic acid level was interpreted as
secondary to hypoperfusion, and intravenous
uid replenishment was continued. Elevated
lactate signals anaerobic metabolism and
indicates sepsis, shock, cardiac arrest, liver
disease, seizure, asthma, trauma, bowel
dysfunction, medication-related damage, or
. Troponin values between 0.04 and
0.39 ng/mL may indicate cardiac problems,
with values over 0.4 ng/mL indicating possible
cardiac arrest. Other reasons for elevation
include sepsis, kidney failure, pulmonary
embolism, myocarditis, drug abuse, or
An elevated body temperature highly
predicts acute infection. Moderate to severe
infections always produce an elevated
temperature, whereas a localized acute apical
abscess with or without swelling will not
Temperatures .101.3F indicate simple
pyrexia, whereas hyperthermia is a term
reserved for body temperatures 105.8F
We initially recorded temperatures in our
patient as high as 106F. Unfortunately, body
temperature was not recorded when the
patient rst arrived. If it had been, a referral
could have occurred sooner.
Although there are no or minor changes
in BP during localized infections, sepsis/septic
shock produce signicant BP changes
attributed to shock, decreased blood volume,
vasodilatation, or severe dehydration (low BP).
Our 23-year-old patient presented with severe
pain, no known medical conditions, a normal
body mass index of 22.8 kg/m
, and elevated
BP readings that steadily decreased to
hypotension by day 2. The normal
physiological heart rate response to infection
and shock is rapid and weak. Our patient had
recorded rates of 100 beats/min and then 160
beats/min before EMS arrival.
Presented is a healthy 23-year-old male whose
condition rapidly deteriorated during an
emergency dental ofce visit due to sepsis/
septic shock. Signicant changes in vital signs
are not expected in localized infections. Hence,
all vital signs should be routinely checked while
examining infected dental patients. BP, pulse,
respiration, and temperature should be
thoughtfully assessed within the context of the
patients overall medical and dental conditions
and sudden alterations in mental state,
respiration, and systolic BP quickly acted on.
The authors thank Dr. Michael A. Steinle for his
valuable input.
The authors deny any conicts of
interest related to this study.
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Oral diseases and associated microbes are a risk factor for systemic diseases and can change the courses of these diseases. To date, epidemiological data on microbial oral infections are scarce, and longitudinal reports are lacking.
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Importance Beginning in 2013, New York State implemented regulations mandating that hospitals implement evidence-based protocols for sepsis management, as well as report data on protocol adherence and clinical outcomes to the state government. The association between these mandates and sepsis outcomes is unknown. Objective To evaluate the association between New York State sepsis regulations and the outcomes of patients hospitalized with sepsis. Design, Setting, and Participants Retrospective cohort study of adult patients hospitalized with sepsis in New York State and in 4 control states (Florida, Maryland, Massachusetts, and New Jersey) using all-payer hospital discharge data (January 1, 2011-September 30, 2015) and a comparative interrupted time series analytic approach. Exposures Hospitalization for sepsis before (January 1, 2011-March 31, 2013) vs after (April 1, 2013-September 30, 2015) implementation of the 2013 New York State sepsis regulations. Main Outcomes and Measures The primary outcome was 30-day in-hospital mortality. Secondary outcomes were intensive care unit admission rates, central venous catheter use, Clostridium difficile infection rates, and hospital length of stay. Results The final analysis included 1 012 410 sepsis admissions to 509 hospitals. The mean age was 69.5 years (SD, 16.4 years) and 47.9% were female. In New York State and in the control states, 139 019 and 289 225 patients, respectively, were admitted before implementation of the sepsis regulations and 186 767 and 397 399 patients, respectively, were admitted after implementation of the sepsis regulations. Unadjusted 30-day in-hospital mortality was 26.3% in New York State and 22.0% in the control states before the regulations, and was 22.0% in New York State and 19.1% in the control states after the regulations. Adjusting for patient and hospital characteristics as well as preregulation temporal trends and season, mortality after implementation of the regulations decreased significantly in New York State relative to the control states (P = .02 for the joint test of the comparative interrupted time series estimates). For example, by the 10th quarter after implementation of the regulations, adjusted absolute mortality was 3.2% (95% CI, 1.0% to 5.4%) lower than expected in New York State relative to the control states (P = .004). The regulations were associated with no significant differences in intensive care unit admission rates (P = .09) (10th quarter adjusted difference, 2.8% [95% CI, −1.7% to 7.2%], P = .22), a significant relative decrease in hospital length of stay (P = .04) (10th quarter adjusted difference, 0.50 days [95% CI, −0.47 to 1.47 days], P = .31), a significant relative decrease in the C difficile infection rate (P < .001) (10th quarter adjusted difference, −1.8% [95% CI, −2.6% to −1.0%], P < .001), and a significant relative increase in central venous catheter use (P = .02) (10th quarter adjusted difference, 4.8% [95% CI, 2.3% to 7.4%], P < .001). Conclusions and Relevance In New York State, mandated protocolized sepsis care was associated with a greater decrease in sepsis mortality compared with sepsis mortality in control states that did not implement sepsis regulations. Because baseline mortality rates differed between New York and comparison states, it is uncertain whether these findings are generalizable to other states.
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The majority of bacteremias do not develop to sepsis: bacteria are cleared from the bloodstream. Oxygen released from erythrocytes and humoral immunity kill bacteria in the bloodstream. Sepsis develops if bacteria are resistant to oxidation and proliferate in erythrocytes. Bacteria provoke oxygen release from erythrocytes to arterial blood. Abundant release of oxygen to the plasma triggers a cascade of events that cause: 1. oxygen delivery failure to cells; 2. oxidation of plasma components that impairs humoral regulation and inactivates immune complexes; 3. disseminated intravascular coagulation and multiple organs' failure. Bacterial reservoir inside erythrocytes provides the long-term survival of bacteria and is the cause of ineffectiveness of antibiotics and host immune reactions. Treatment perspectives that include different aspects of sepsis development are discussed.
Sepsis is a life-threatening organ dysfunction that results from the body's response to infection. It requires prompt recognition, appropriate antibiotics, careful hemodynamic support, and control of the source of infection. With the trend in management moving away from protocolized care in favor of appropriate usual care, an understanding of sepsis physiology and best practice guidelines is critical.
Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes.
The autonomic cardiovascular control was investigated in 10 patients with septic shock, 10 patients with sepsis syndrome, and six tilted healthy subjects. Overall variability, high- and low-frequency components (AUC, HF, and LF, beats/min(2)/Hz or mm Hg-2/Hz) from heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures spectra were obtained from 5-min recordings. LFHR/HFHR and the square root of LFSBP/LFHR (alpha) were used as indices of sympathovagal interaction and baroreflex control of the heart, respectively. Compared with tilted control subjects and patients with sepsis syndrome, septic shock is characterized by reduction in: (1) HR variability, i.e., decreased AUC(HR) (p = 0.007), LFHR (p = 0.002), and LFHR/HFHR (p = 0.0002); (2) DBP variability, i.e., decreased AUC(DBP) (p = 0.003) and LFDBP (p = 0.001), (3) or (p = 0.003). In septic shock, LFHR/HFHR, alpha, and LFDBP correlated with mean blood pressure (r = 0.67, p = 0.04, r = 0.64, p = 0.03, and r = 0.88, p = 0.0008, respectively), and with plasma norepinephrine levels (r = -0.65, p = 0.03, r = -0.79, p = 0.006, and r = -0.69, p = 0.03, respectively). In conclusion, onset of septic shock is characterized by high concentrations of circulating catecholamines but impaired sympathetic modulation on heart and vessels, suggesting that central autonomic regulatory impairment contributes to circulatory failure.
Available data do not support the concept that leukocytes engulf and kill bacteria in the bloodstream. Leukocytes cannot recognize or engulf bacteria in flowing blood; therefore, phagocytosis is impossible in the bloodstream and occurs instead outside of the bloodstream in the body tissues. Erythrocytes capture bacteria in the circulation using an electric charge and kill them using oxidation. The dead bacteria are then disintegrated and digested by the reticuloendothelial system (RES), particularly in the liver and the spleen
Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.Objective To evaluate and, as needed, update definitions for sepsis and septic shock.Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant.Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.
Rationale: Reducing the global burden of sepsis, a recognised global health challenge, requires comprehensive data on the incidence and mortality on a global scale. Objective: To estimate the worldwide incidence and mortality of sepsis and to identify knowledge gaps based on available evidence from observational studies. Methods: We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years. Main results: The search yielded 1553 reports from 1979 to 2015, of which 45 met our criteria. 27 studies from 7 high-income-countries provided data for meta-analysis. For these countries, the population incidence rate was 288 [95%CI, 215-386, τ=0.55] hospital-treated sepsis cases and 148 [95%CI, 98-226, τ=0.99] hospital-treated severe sepsis cases per 100 000 person-years. Restricted to the last decade, the incidence rate was 437 [95%CI, 334-571, τ=0.38] sepsis and 270 [95%CI, 176-412, τ=0.60] severe sepsis cases per 100 000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income-countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income-country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually. Conclusions: Population-level epidemiological data for sepsis are scarce, and non-existent for low- and middle-income-countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality - particularly in low- and middle-income-countries.
Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This depression is associated with the presence of a circulating myocardial depressant substance with physical characteristics consistent with cytokines. The present study utilized an in vitro myocardial cell assay to examine the role of various human recombinant cytokines, including tumor necrosis factor (TNF)alpha and interleukin (IL)1beta, in depression of cardiac myocyte contractile function induced by serum from humans with septic shock. The extent and velocity of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed loop video tracking system. Individually, TNF-alpha and IL-1beta each caused significant concentration-dependent depression of maximum extent and peak velocity of myocyte shortening in vitro. In combination, TNF-alpha and IL-1beta induced depression of myocardial cell contractility at substantially lower concentrations consistent with a synergistic effect. Using immunoabsorption, removal of both TNF-alpha and IL-1beta (but not either alone) from the serum of five patients with acute septic shock and marked reversible myocardial depression resulted in elimination of serum myocardial depressant activity. IL-2, -4, -6, -8, -10, and interferon gamma failed to cause significant cardiac myocyte depression over a wide range of concentrations. These data demonstrate that TNF-alpha and IL-1beta cause depression of myocardial cell contraction in vitro and suggest that these two cytokines act synergistically to cause sepsis-associated myocardial depression in humans.