Journal of Critical Care 71 (2022) 154098

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Journal of Critical Care

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The incidence of propofol infusion syndrome in critically-ill patients

Wai Kin Li a,⁎, Xian Jie Cindy Chen a, Diana Altshuler a,b, Shahidul Islam a, Peter Spiegler a,
Liane Emerson a, Michael Bender a
a
New York University Langone Hospital – Long Island, NY, USA
b
New York University Langone Health, NY, USA

a r t i c l e i n f o a b s t r a c t

Keywords: Purpose: PRIS is a potentially fatal syndrome characterized by various clinical symptoms and abnormalities. Ex-
Propofol perts suggest that propofol treatment duration ≥48 h or dose ≥83 μg/kg/min is associated with developing
Sedation PRIS. We hypothesized PRIS might be underdiagnosed due to the overlap of PRIS clinical manifestations with crit-
Anesthesia ical illnesses.
Critical care
Materials and methods: Multihospital, retrospective study of adult patients who received continuous propofol
Intensive care unit
Mechanical ventilation
infusion ≥48 h or dose ≥60μg/kg/min for >24 h since admission were assessed for the development of PRIS.
Results: The incidence of PRIS was 2.9% with a PRIS-associated mortality rate of 36.8%. In PRIS patients, propofol
was administered at a median dose of 36.4 μg/kg/min and over a median duration of 147.0 h. The development
of PRIS was observed at a median of 125.0 h post-propofol initiation and a cumulative dose of 276.5 mg/kg.
The development of metabolic acidosis (78.9%), cardiac dysfunction (52.6%), hypertriglyceridemia (100%), and
rhabdomyolysis (26.3%) were observed in our PRIS patients.
Conclusion: PRIS can often be overlooked and underdiagnosed. It is important to monitor for early signs of PRIS
in patients who are on prolonged propofol infusion. Prompt recognition and interventions can minimize the
dangers resulting from PRIS.
© 2022 Elsevier Inc. All rights reserved.

1. Introduction tachycardia, ventricular tachycardia, ventricular fibrillation), hypotension,

Propofol, a highly lipophilic anesthetic agent formulated in a 10%
lipid emulsion, is commonly used in the intensive care setting to facili-
tate sedation, ventilator synchrony, and optimize oxygenation in pa-
tients receiving mechanical ventilation and in patients experiencing
refractory status epilepticus [1-4]. Propofol's appeal in critically-ill pop-
ulations owes to its fast onset and short duration of action [1,2]. Propofol
potentiates its effect in the brain by stimulating γ-aminobutyric acid
(GABA) receptors, leading to hyperpolarization of the neuronal cell mem-
brane and inhibiting action potential firing [1,2]. Propofol administration
is associated with significant adverse effects such as bradycardia, hypo-
tension, respiratory depression, hypertriglyceridemia, and propofol infu-
sion syndrome (PRIS).
The term “PRIS” was first used by Bray in 1998 [3]; is characterized by
a wide range of clinical symptoms and abnormalities such as metabolic
and lactic acidosis, cardiac dysfunction (including right bundle branch
block, Brugada-like syndrome, atrial fibrillation, supraventricular
⁎ Corresponding author at: NYU Langone Hospital, Long Island, 259 First Street,
Mineola, NY 11501, USA.
E-mail address: waikin.li@nyulangone.org (W.K. Li).
rhabdomyolysis, acute kidney injury (AKI), lipidemia, liver failure, hepa-
tomegaly, and electrolyte abnormalities [4-6]. The manifestations of
PRIS can overlap with many common critical illnesses such as sepsis,
hemophagocytic lymphohistiocytosis, shock, acute kidney and liver fail-
ure, metabolic acidosis, and seizures. Moreover, it is proposed that con-
comitant administration of vasopressors or corticosteroids with propofol
may be risk factors for PRIS development [7-9]. While it is challenging
to distinguish PRIS from these critical illnesses, researchers attempted to
address the issue to determine the true incidence of PRIS. However,
these studies were designed with differences in inclusion and exclusion
criteria, patient population, study period and contained varying def-
initions of PRIS. In 2009, Robert et al. evaluated 1017 critically-ill pa-
tients receiving propofol infusion for longer than 24 h and reported
the incidence of PRIS to be 1.1% [10]. Later, Diaz et al. evaluated 72
critically-ill patients receiving propofol for longer than 72 h and
found a higher incidence at 4.1% [11]. Data from case reports and
case studies may be inaccurate or misinterpreted due to omitted
data or estimation of missing values [4]. The lack of consistency in
data collection, transcription errors, and various ICU practices
among institutions could affect the relevance to today's practice.
Therefore, the true incidence of PRIS remains unknown.

https://doi.org/10.1016/j.jcrc.2022.154098
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W.K. Li, X.J.C. Chen, D. Altshuler et al.
During the coronavirus 2019 (covid-2019) pandemic, propofol was
one of the most commonly used sedatives. High doses of propofol and
prolonged infusions were often used to achieve deep sedation in
critically-ill patients with acute respiratory distress syndrome (ARDS)
[12,13]. Therefore, we took this opportunity in hopes to provide an ac-
curate assessment of the incidence of PRIS throughout the New York
University (NYU) Langone Health System. We hypothesized PRIS
might be underdiagnosed due to some of the manifestations of PRIS
overlaps with other critical illnesses [7,14] and the recognition of this
syndrome caused by propofol may be under-appreciated.
2. Materials and methods
2.1. Study design
We performed a retrospective, multihospital observational cohort
study of adult patients admitted to the NYU Langone Health System be-
tween March 1, 2020, and February 28, 2021, to evaluate the incidence
of PRIS in critically-ill patients admitted to the ICU. The NYU Langone
Institutional Review Board approved the study (i20–01638).
Patients were included if they were admitted to any of the four hos-
pitals within the health system, were ≥18 years old, and received con-
tinuous propofol infusion ≥48.0 h or dose ≥60.0 μg/kg/min for >24 h
since admission. Patients were excluded if they had developed hypertri-
glyceridemia or rhabdomyolysis prior to propofol infusion. Hypertri-
glyceridemia is characterized by serum triglycerides greater than the
upper normal limit (0–149 mg/dL) and rhabdomyolysis is defined by
creatinine phosphokinase (CPK) level greater than the upper normal
limit (29–168 IU/L) based on our hospital laboratory's parameters.
We have a standardized health system-wide protocol for sedation
administration in the ICU. Propofol and dexmedetomidine are the seda-
tive agents of choice in our ICU. These medications are prescribed by li-
censed independent practitioners and are titrated by nurses to a
Richmond Agitation-Sedation Scale (RASS) score of 0 to −2; targeting
light sedation for most patients. The RASS score is documented every
2 h. Medication order-set are prebuilt into the electronic health record
and the dosing for propofol ranges from 5 to 75 μg/kg/min and
dexmedetomidine ranges from 0.2 to 1.5 μg/kg/h and guidance for nurs-
ing to titrate the medication is embedded in the order. If higher doses
are indicated, it will require modification of the order by the licensed
practitioner and titration will be done off protocol by the licensed prac-
titioner. During the peak of COVID, propofol doses were titrated to meet
the higher RASS score for the management of ARDS.
The primary endpoint was to assess the incidence of PRIS. Our study
adapted commonly used PRIS criteria previously identified [4-6,10]. We
selected six PRIS-associated clinical manifestations and separated them
into major and minor clinical manifestations. There are two definitions
of PRIS in our study. The first definition label “PRIS ONE” is defined by
meeting both major clinical manifestations (cardiac dysfunction &
metabolic acidosis) PLUS two or more minor clinical manifestations.
The second definition label as “PRIS TWO” was defined by meeting
one or none of the major clinical manifestations PLUS three or
more minor clinical manifestations. All patients must have devel-
oped hypertriglyceridemia or rhabdomyolysis as part of their
minor criteria as both are more specific manifestations of PRIS
(Table 1). Given that manifestations of metabolic acidosis, cardiac
dysfunction, acute kidney injury and hepatic transaminitis can
occur in covid patients, we restricted that all PRIS patients must
have developed rhabdomyolysis OR hypertriglyceridemia as one of
their clinical manifestations (Table 1), as both are more likely to be
caused by propofol infusion [15].
The major clinical manifestations were metabolic acidosis and car-
diac dysfunction, given both are the two common distinguishing fea-
tures of PRIS documented in published case reports and reviews.
Metabolic acidosis was defined by arterial blood gas pH < 7.35 and
serum bicarbonate <22 mEq/L3 and cardiac dysfunction were
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Journal of Critical Care 71 (2022) 154098
Table 1
Definition of PRIS.
PRIS is defined by two definitions: PRIS ONE and PRIS TWO.
PRIS Definition Major Criteria Minor Criteria
PRIS ONE¥ Meeting ALL PLUS Meeting two or more
• Cardiac dysfunction • Rhabdomyolysis
• Metabolic acidosis • Hypertriglyceridemia
• Acute kidney injury
• Hepatic transaminitis
PRIS TWO¥ Meeting 1 or none PLUS Meeting three or more
• Cardiac dysfunction • Rhabdomyolysis
• Metabolic acidosis • Hypertriglyceridemia
• Acute kidney injury
• Hepatic transaminitis
¥ Rhabdomyolysis and/or hypertriglyceridemia must be present as one of the minor
criteria.
characterized by widening of the QRS complex (≥20 ms), new onset of
atrial fibrillation, ventricular tachycardia, electrocardiogram (ECG)
changes, cardiac arrest while on propofol, decreased ejection fraction
from baseline, and refractory bradycardia [10].
The minor clinical manifestations included rhabdomyolysis (CPK ≥
5000 IU/L) hypertriglyceridemia (serum triglycerides ≥400 mg/dL),
AKI, and hepatic transaminitis [4-6,10]. Patients were screened carefully
for the development of rhabdomyolysis and hypertriglyceridemia while
on propofol therapy to ensure that they were not on concomitant med-
ications (statins, daptomycin, fibrates, clevidipine, and parenteral lipid
emulsions), trauma and surgeries that may cause the elevation of CPK
and serum triglycerides. If patients while on propofol therapy devel-
oped hypertriglyceridemia or rhabdomyolysis thought to be due to
concomitant medications, surgery and trauma, these patients were
excluded from PRIS. AKI was represented by an increase in serum
creatinine >0.3 mg/dL or >50% from baseline [16] and hepatic
transaminitis was described by an increase in aspartate aminotrans-
ferase (AST) and/or alanine aminotransferase (ALT) ≥ 3 times above
baseline. Each patient's laboratory value and medical notes were
thoroughly reviewed manually by two separate data collectors to
ensure that the development of each of the clinical manifestations
of PRIS is captured accurately.
2.2. Study variables
Data were extracted from the NYU Langone Health Covid-19 clinical
data mart and manual chart review. Demographic variables included
age, weight, gender, body mass index (BMI), race, past medical history,
surgeries, trauma, and weighted Elixhauser score. Comorbidity status
was determined using Elixhauser's algorithm based on ICD-9-CM and
ICD-10 diagnosis codes [17,18]. R-package “comorbidity” (https://cran.
r-project.org/) was applied to compute the comorbidity indices.
Laboratory variables include arterial blood gas, serum triglycerides,
serum potassium, serum creatinine, serum bicarbonate, creatinine
phosphokinase, liver enzymes, and medications administered including
vasopressors, corticosteroids, and other concomitant medications.
Treatment duration and propofol dosing were manually collected
through an electronic chart review to ensure accuracy. ECGs and cardi-
ology consultant notes were reviewed for the presence or absence of
cardiac abnormalities.
2.3. Outcomes
The primary outcome of this study is to assess the incidence of PRIS.
The secondary outcomes include PRIS-associated mortality and hospital
length of stay. PRIS-associated mortality was defined by death within
seven days after the development of PRIS and hospital length of stay is
determined by the number of days the patients spent in the hospital
until discharge or death, whichever occurred first.
W.K. Li, X.J.C. Chen, D. Altshuler et al. Journal of Critical Care 71 (2022) 154098

2.4. Statistical analysis
The incidence of PRIS was computed along with a 95% confidence in-
terval (CI) using the exact Clopper-Pearson method. Continuous vari-
ables were summarized and presented using median (interquartile
range-IQR) and categorical variables using frequency (percentage).
The normality of the variables was assessed using histograms, Q-Q
plots, and a formal Kolmogorov-Smirnov test. Continuous variables
were compared between PRIS and non-PRIS groups using Wilcoxon
rank-sum test, and categorical variables using Chi-square or Fisher's
exact test as appropriate. SAS 9.4 and R 4.0.4 were used to conduct all
analyses.
3. Results
3.1. Enrollment and patient demographics
Between March 1st, 2020 to February 28th, 2021, 654 patients met
the study criteria and were included in the analysis. Baseline character-
istics (n = 654) are provided in Table S1 (supplementary material). The
majority of these patients were male (71.4%), with a median age of 63.0
years (IQR, 53.0–71.0), a median weight of 81.6 kg (IQR, 72.5–94.9), a
median weighted Elixhauser score of 23.0 (IQR, 14.0–33.0) and admit-
ted to medical ICU service (83.8%). Out of 654 patients, 504 patients
(77.1%) were covid-19 positive. In terms of infusion parameters,
the median dose of propofol was 32.4 μg/kg/min (IQR, 24.5–40.4),
which was given over a median treatment duration of 113.0 h
(IQR, 72.0–178.0), at a median cumulative dose of 208.0 mg/kg (IQR,
128.0–373.0). Serum triglycerides and CPK values were available in
573/654 (87.6%) patients and 510/654 (77.9%) patients. The overall
mortality rate in our cohort (PRIS & non-PRIS) was 57.3% and the
median hospital length of stay was 21.0 days (IQR, 12.0–35.0).
3.2. Outcomes
PRIS was identified in 19 out of 654 patients, at an incidence of 2.9%
(95% CI, 1.8%–4.5%). Of the 19 PRIS patients, 10 patients met PRIS ONE
criteria and 9 patients met PRIS TWO criteria. In PRIS patients, propofol
was administered at a median dose of 36.4 μg/kg/min (IQR, 30.3–40.0),
a median duration of 147.0 h (IQR, 100.0–190.0) and a median cumula-
tive dose of 307.1 mg/kg (IQR, 198.3–432.0, see Table 2). The develop-
ment of PRIS was observed at 125.0 h (IQR, 69.0–190) post-propofol
initiation (Fig. 1), and the total cumulative dose received at the time
of PRIS development was 276.5 mg/kg (IQR, 150.8–420.2) (Table 3).
Propofol was discontinued in 7/19 (37%) patients. In the seven patients
in whom propofol was discontinued, four (57%) were noted to have im-
proved laboratory parameters after propofol was stopped and one sur-
vived. In the non-PRIS group, the median dose of propofol was 32.2
μg/kg/min (IQR, 23.8–40.5) with a median treatment duration of
111.0 h (IQR, 71.0–178.0); cumulative propofol dose of 202.7 mg/kg
(IQR, 126.5–371.8). Non-PRIS patients had a median hospital length of
stay of 21.5 days (IQR, 12.0–35.0) and a mortality rate of 56.2% (Table 2).
We observed the development of hypertriglyceridemia and AKI in all
patients with PRIS (Table 3). Hypertriglyceridemia occurred at a median
onset of 4.6 days (IQR, 2.3–6.3) post propofol infusion; serum triglycer-
ides were elevated at a median level of 482.0 mg/dL (IQR, 437.0–601.0).
The incidence of metabolic acidosis and cardiac dysfunction occurred in
15 (78.9%) patients and 10 (52.6%) patients, respectively. Recognized
cardiac dysfunctions included ventricular tachycardia, bundle branch
block, new onset of atrial fibrillation, widening of the QRS interval,
and ST-elevation changes (Table 4). Five PRIS patients developed
elevated CPK at a medium onset of 4.7 days (IQR, 3.6–9.3) post propofol
infusion, with a median serum CPK was 8298.0 IU/L (IQR, 5840.0-
14,718.0).
The overall mortality rate in our PRIS group was 94.7% and PRIS-
associated mortality was 36.8% (n = 7/19). The median hospital length
of stay was 16.0 days (IQR, 9.0–30.0) and the median ICU length of stay
was 14.0 days (IQR, 8.0–18.0) (Table 2). Concomitant vasopressor and
glucocorticoid use in PRIS patients on propofol therapy was 84.2% (16/
19) and 42.1% (8/19), respectively (Table 3).
4. Discussion
In our retrospective study, the incidence of PRIS was 2.9% with an as-
sociated mortality rate of 36.8%. PRIS is a potentially fatal syndrome
characterized by a spectrum of clinical symptoms and abnormalities in-
cluding hypotension, cardiac arrhythmias, metabolic and lactic acidosis,
electrolytes abnormalities, rhabdomyolysis, AKI, hypertriglyceridemia,

Table 2
All data are displayed as n (%) unless otherwise noted.

Baseline characteristics PRIS Non-PRIS P-value1

(N = 19) (N = 635)

Age (year) 64.0 (48.9–71.9) 63.2 (53.2–71.2) 0.726

(Median, Q1–Q3)
Male gender 15.0 (78.9) 452.0 (71.1) 0.609
BMI (kg/m2) 27.4 (26.6–30.7) 28.7 (25.8–33.5) 0.734
(Median, Q1–Q3)
Weight (kg) 81.6 (74.8–98.7) 81.6 (72.5–94.6) –
(Median, Q1–Q3)
Hypertension 13.0 (68.4) 441.0 (69.4) 0.924
Diabetes 8.0 (42.1) 241.0 (38.0) 0.714
Congestive heart failure 1.0 (5.3) 163.0 (25.7) 0.056
Chronic pulmonary disease 1.0 (5.3) 165.0 (26.0) 0.057
Renal failure 3.0 (15.8) 185.0 (29.1) 0.304
Liver disease 4.0 (21.1) 139.0 (21.9) 1
Weighted Elixhauser score (AHRQ) 22.0 (15.0–26.0) 23.0 (14.0–34.0) 0.366
(Median, Q1–Q3)
Hospital length of stay (day) 16.0 (9.0–30.0) 21.5 (12.0–35.0) 0.098
(Median, Q1–Q3)
Overall mortality 18.0 (94.7) 357.0 (56.2) <0.001
PRIS-associated mortality 7.0 (36.8) – –
COVID 18.0 (94.7) 486.0 (76.5) 0.092
Infusion dose (mcg/kg/min) 36.4 (30.3–40.0) 32.2 (23.8–40.5) 0.102
(Median, Q1–Q3)
Infusion duration (hours) 147.0 (100.0–190.0) 111.0 (71.0–178.0) 0.152
(Median, Q1–Q3)
Cumulative dose (mg/kg) (Median, Q1–Q3) 307.1 (198.3–432.0) 202.7 (126.5–371.8) 0.05

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Paent 19 147
Paent 18 69
Paent 17 64
Paent 16 56
Paent 15 346
Paent 14 113
Paent 13 79
Paent 12 125
Paent 11 190
Paent 10 49
Paent 9 159
Paent 8 194
Paent 7 150
Paent 6 72
Paent 5 48
Paent 4 192
Paent 3 216
Paent 2 80
Paent 1 168

0 50 100 150 200 250 300 350 400

Time (Hours)

Fig. 1. Time to the development of PRIS (n = 19).

The development of PRIS relative to the start of propofol administration. PRIS = propofol infusion syndrome.

hepatomegaly, and acute liver failure [4-6]. Studies of PRIS tend to be PRIS in critically-ill patients revealed an incidence of 1.1%, which was as-
published as case reports compiled in literature reviews. While there sociated with both a shorter duration and lower propofol dose than pre-
is no universal standard definition of PRIS, experts suggest that propofol viously described, translating into a mortality rate of 18% [10].
treatment duration ≥48.0 h or a propofol dose ≥83.0 μg/kg/min (5 Our study was conducted in a single, multihospital health system,
mg/kg/h) is associated with developing PRIS [4,5]. Several structured lit- over a defined time period. Data were extracted from the clinical data-
erature review and analyses of published case reports concludes that base and through a chart review of the electronic health records.
the mortality rate from PRIS could be as high as 30%–51% [4,5,19]. Propofol titration and sedation goals were practiced under the guidance
Limitations of prior PRIS studies include a lack of consistency in data of the hospital's protocol and guideline recommendations [20,21]. We
collection, missing values, transcribing errors, and the varied publication congregated common clinical manifestations that were used to define
period, which could affect the relevance to present-day practice. For in- PRIS with our adaptations. PRIS is defined by the development of meta-
stance, a more recent prospective observational multicenter study of bolic acidosis, cardiac dysfunction, acute kidney injury, liver failure,
rhabdomyolysis, and hypertriglyceridemia. Given that majority of the
Table 3 studied population were infected with covid-19, we looked to further
All data are displayed as n (%) unless otherwise noted. minimize the masking effect of covid-19 by refining the definition of
PRIS where we required the development of hypertriglyceridemia or
Characteristics of PRIS Patients (n = 19)
rhabdomyolysis – two distinctive features of PRIS which are not univer-
Number of patients meeting PRIS ONE criteria 10.0 (52.6)
sally observed in covid-19 infection – to be present in all of the PRIS pa-
Number of patients meeting PRIS TWO criteria 9.0 (47.3)
The incidence of each clinical manifestation tients [15]. Hypertriglyceridemia (serum triglycerides >400 mg/dL) is a
Metabolic acidosis 15.0 (78.9) hallmark characteristic of PRIS and serum triglycerides have been sug-
Cardiac dysfunction 10.0 (52.6) gested as a biomarker to monitor its development [3-6,10,11,14,19].
Hypertriglyceridemia 19.0 (100.0) Rhabdomyolysis, another characteristic of PRIS, has been highlighted
Rhabdomyolysis 5.0 (26.3)
Acute kidney injury 19.0 (100.0)
and reported in the literature [4-7,10,11,19,22,23]. CPK values <5000
Hepatic transaminitis 15.0 (78.9)
The onset of hypertriglyceridemia (Days) 4.6 (2.3–6.3)
(Median, Q1–Q3) Table 4.
Serum triglycerides (mg/dL) (Median, Q1–Q3) 482.0 (437.0–601.0) All data are displayed as n (%) unless otherwise noted.
The onset of rhabdomyolysis (Days) (Median, Q1–Q3) 4.7 (3.6–9.3)
Characteristics of Cardiac Dysfunction in PRIS patients (n = 10)
Serum creatinine phosphokinase (IU/L) 8298.0 (5840.0–14,718.0)
(Median, Q1–Q3) Ventricular Tachycardia 4 (40)
Concomitant use of steroids 8.0 (42.1) New onset of Atrial Fibrillation 3 (30)
Concomitant use vasopressor 16.0 (84.2) Bundle Branch Block 2 (20)
The onset of PRIS (Hours) (Median, Q1–Q3) 125.0 (69.0–190.0) Pulseless electrical activity while on propofol 3 (30)
Total cumulative dose at the onset of PRIS (mg/kg) 276.5 (150.8–420.2) QRS Widening 1 (10)
(Median, Q1–Q3) ST-Elevation 1 (10)

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W.K. Li, X.J.C. Chen, D. Altshuler et al.
IU/L in patients receiving propofol eliminated the possibility for the
development of PRIS in one study [23]. According to our stringent
definition of PRIS, patients must have developed hypertriglyceridemia
and/or rhabdomyolysis with an elevated level of CPK > 5000 IU/L
post-propofol administration from their normal baseline. The require-
ment for the presence of hypertriglyceridemia and rhabdomyolysis in
our study's definition of PRIS strengthens our ability to accurately report
the incidence of PRIS.
In the past, propofol infusion ≥48.0 h, dose ≥83.0 μg/kg/min, and/or
cumulative dose have been reported as risk factors for developing
PRIS with the median time of onset thought to be three days [4,10].
The total cumulative dose of propofol has been demonstrated to be
linearly associated with the numbers of the clinical feature of PRIS in-
volved and the median cumulative dose observed was 380.4 mg/kg
[4]. In our PRIS patients, the median dose and duration of propofol
was 36.4 μg/kg/min, and 147.0 h respectively, with a median time to de-
velopment of PRIS at 125.0 h (IQR, 69.0–190.0) post propofol infusion.
Our PRIS patients received a median total cumulative propofol dose of
307.1 mg/kg (IQR, 198.3–432.0) and at the time to the development of
PRIS the median cumulative dose of propofol received was 276.5
mg/kg (IQR, 150.8–420.2). Our study suggests that PRIS can occur at a
lower infusion dose and lower cumulative dose. Moreover, we observed
PRIS occur ≥48.0 h post propofol administration. The time to develop-
ment of PRIS in our study was longer with 125.0 h versus 72.0 h in
one of the studies where 82% of their PRIS patients received a dose
<83 μg/kg/min [4,10]. This difference could be due to our PRIS criteria
requiring a combination of PRIS clinical manifestations and also
constraining specific clinical manifestation (hypertriglyceridemia and/
or rhabdomyolysis) to be present in comparison to early definitions
that were used [10]. We observed the hospital length of stay –.
defined as a number of days until hospital discharge or death – is
shorter in our PRIS group compared to the non-PRIS group (16.0 days
vs 21.5 days), which reflects the very high overall mortality rate in our
PRIS group.
The overall mortality rate in our PRIS group was found to be 97%.
While the mortality rate might not be directly related to PRIS, it can
be inflated given many of our patients (94.7%) were infected with
covid-19. Therefore, we tried to minimize the confounding effect of
covid-19 by further examining the death in the PRIS group and defining
PRIS-associated death only if the patient died within 7 days after the
development of PRIS. Through this approach, we report a mortality
rate associated with PRIS of 36.8%.
Some have proposed other risk factors leading to the development of
PRIS including concomitant usage of vasopressors or steroids
[7,22,24,25]. It is thought that steroids can cause rhabdomyolysis,
which leads to metabolic acidosis and acute renal failure [25]. Also vaso-
pressors are known to increase vascular tone and the use of vasopres-
sors with propofol can lead to a vicious cycle of progressive
myocardial depression precipitating into arrhythmias and cardiac dys-
function. In our study, we observed 42.1% (8/19) and 84.2% (16/19)
PRIS patients' who received steroids and vasopressors respectively.
While we observed PRIS in patients with concomitant usage of vaso-
pressors and steroids with propofol, we can't accurately confirm the di-
rect association of these medications, as our study was not power to
detect this. Further studies with this specific focus are needed to con-
firm the role of vasopressor and steroids in the development of PRIS.
PRIS was first reported 30 years ago with a high fatality rate, this
syndrome has continued to be overlooked. While treatment guidelines
recommend monitoring for hypertriglyceridemia, bradycardia, and lac-
tic acidosis in patients receiving propofol therapy, it is unclear at which
point clinicians should begin to monitor for signs of PRIS and when an
alternative sedative agent should be used [26]. This is evidenced in
our study as only seven out of 19 propofol orders were discontinued
after PRIS development. There was only one documented suspicion of
PRIS and the propofol infusion was switched to an alternative sedative.
It is unclear whether PRIS was unrecognized for these patients. Among
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Journal of Critical Care 71 (2022) 154098
the seven patients, four demonstrated laboratory improvement after
stopping propofol and one survived. This highlights the fact that early
detection and intervention can prevent the progression of PRIS and
death.
There are several strengths to our study as it was conducted through
a uniformed multihospital health system over a specific time period.
Therefore, our study includes a diverse patient population from various
communities while maintaining a consistent dosing strategy, medica-
tion availability, a uniform delivery of continuous medication, and con-
sistent laboratory parameters in all patients. This ensures that our
patients received similar levels of care across all hospital centers, elimi-
nating disparity among sedation therapies, dosing weight, and sedation
goals.
There are a few limitations to our study, the incidence of PRIS may be
underreported in our study due to the stringent PRIS definition em-
ployed. Not all patients in the dataset had triglyceride (12.4%) and
CPK (22.1%) values collected, but both were required to identify a pa-
tient with PRIS. Our study's design is limited to its retrospective and ob-
servational nature and may not be ideal to capture a mortality rate from
PRIS, however, a prospective study design would not be suitable to
study mortality either, as urgent propofol discontinuation is required
once this fatal syndrome is identified. We acknowledge that our PRIS-
associated mortality rate might be confounded by covid-19 as 77.1% of
the patients were covid-19 positive. Although the mortality rate is not
the principal focus of assessment in our study, we made an effort to
eliminate the confounding effects of covid-19 by associating death due
to PRIS in those who only died within seven days after the development
of the syndrome. Our detected PRIS mortality rate is consistent with
previously reported literatures [5,19].
5. Conclusion
In summary, our retrospective observational study found that the
prevalence of PRIS was 2.9% with a PRIS-associated mortality rate of
36.8%. PRIS can often be overlooked and underdiagnosed. Clinicians
and pharmacists should be vigilant in recognizing signs of PRIS in pa-
tients who are on prolonged propofol infusion as prompt recognition
and interventions can minimize the dangers resulting from PRIS.
The study was conducted at NYU Langone Health System.
Author's contribution
WKL and XJCC are co–first authors.
WKL- Conceptualization, Methodology, Writing-Original Draft,
Investigation, Visualization, Project administration.
XJCC- Conceptualization, Methodology, Writing-Review & Editing,
Supervision, Project administration.
DA- Conceptualization, Methodology, Writing-Review & Editing.
SI- Formal analysis, Data Curation, Resources.
PS- Conceptualization, Writing - Review & Editing.
LB- Investigation, Validation.
MB- Conceptualization, Methodology, Project administration,
Writing-Review & Editing.
All authors contributed to the authorship and editing of the article.
All reviewed and interpreted the data. There are no disclosures related
to this research.
Declaration of Competing Interest
This research received no specific grant from any funding agency in
the public, commercial, or not-for-profit sectors.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.jcrc.2022.154098.
W.K. Li, X.J.C. Chen, D. Altshuler et al.
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