Introduction
Propofol (2,6-diisopropylphenol) sedation for endoscopic procedures is increasing
in use [1]
[2]. Because propofol is highly lipophilic and crosses the blood-brain barrier quickly
it has a rapid onset of action. In addition, its short half-life (2 – 4 minutes) results
in rapid post-procedure recovery [3]
[4]. The ability to provide rapid and safe moderate sedation to perform endoscopic procedures
has made it a highly desirable sedative option for both physicians and patients [5]
[6]
[7].
Propofol sedation, when administered under the guidance of a physician who is not
an anesthesiologist, is defined as non-anesthesiologist administered propofol (NAAP).
Propofol when used in combination with an opioid agent such as fentanyl is termed
balanced propofol sedation (BPS) and results in optimal moderate sedation and amnestic
effect allowing for thorough evaluation and endoscopic intervention [8]. A joint statement issued in 2009 by all the four US gastrointestinal professional
societies stated “The administration of propofol and standard sedation by non-anesthesiologists
is comparable with respect to their efficacy and safety profiles. Proper training
and patient selection are crucial for the safe practice of NAAP sedation” [9].
Propofol sedation has been shown to be safe for numerous surgical procedures and for
patients on mechanical ventilation. Initial reports of safe propofol sedation in ICU
patients on mechanical ventilation were published over 30 years ago, including patients
with higher American Society of Anesthesiologists risk class (ASA) [10]
[11]
[12]. More recent studies have established the safety and effectiveness of NAAP for both
standard and advanced endoscopic procedures; these studies were performed in the outpatient
setting in patients with relatively low ASA risk class and lower severity of illnesses
[13]
[14]
[15]
[16]. There is greater concern regarding the safety of NAAP sedation for digestive endoscopy
in hospitalized patients with a higher number of comorbidities and greater severity
of illness [17].
Of significant importance, to date there have been no prior studies evaluating the
safety of NAAP sedation for digestive endoscopy in hospitalized patients, especially
patients admitted to an intensive care unit (ICU). This is a critical gap in knowledge
regarding the safety of NAAP sedation in ICU patients undergoing endoscopy. Our institution
routinely performs endoscopic procedures using NAAP in a variety of inpatient and
outpatient settings. The aim of our study was to evaluate the safety and efficacy
of non-anesthesiologist- administered Propofol (NAAP) sedation for esophagogastroduodenoscopies
(EGDs) performed in acutely ill patients with gastrointestinal bleeding in an Intensive
Care Unit (ICU) setting.
Methods
Study design
A retrospective chart review was performed on all EGDs performed in the medical, surgical,
cardiovascular, and neurosurgical ICUs at a single, tertiary care referral center
from June 2014 to September 2016 after obtaining Institutional Review Board approval.
Inclusion/exclusion criteria
Patients having an EGD for gastrointestinal bleeding using NAAP sedation in the ICU
were included in our study. Patients were excluded if they were on mechanical ventilation
or on vasopressor support (dopamine, dobutamine, epinephrine, norepinephrine, phenylephrine,
or vasopressin). Patients on vasopressors or mechanical ventilation were excluded
to avoid confounding results as our primary outcome measured was sedation related
cardiovascular and pulmonary complications.
NAAP sedation in EGDs performed in ICU
NAAP was performed on all the procedures under endoscopist guidance and administered
by the ICU nurses per our institutional protocol. ICU nurses and gastroenterology
endoscopy providers at our institution are certified in advanced cardiac life support
(ACLS) and Basic Life Support (BLS) and undergo a sedation training program (Safe
Sedation Training, Applied Medical Visualizations) which includes airway measures,
drug administration and rescuing patients from inadvertent deep sedation. Recertification
is required every 2 years. New nursing staff are further required to administer sedation
and documentation under supervision by a senior nurse prior to working independently.
Five people were present during endoscopy. Personnel present for all EGD procedures
included two ICU nurses, an endoscopy lab technician, attending gastroenterologist,
and a gastroenterology fellow per institutional policy. One nurse administered medications
and the second nurse charted medications administered, vital signs, and any interventions
including those performed for hemodynamic and respiratory decompensation. All patients
were administered supplemental oxygen by nasal cannula per standard protocol. An initial
induction dose of fentanyl usually (12.5 – 25 mcg) and propofol (20 – 30 mg) was given
with subsequent administration of propofol of 10 to 30 mg every 2 to 3 minutes to
ensure adequate and sustained moderate sedation to allow completion of the procedure
per the endoscopists’ discretion. Patients had continuous pulse oximetry and continuous
heart rate monitoring using a five-lead electrocardiogram monitor. Blood pressures
were recorded every 2.5 to 3 minutes per institutional standard protocol. Pro-motility
agents (e. g. erythromycin IV) are not routinely given prior to EGD procedures at
our institution.
Data sources and measures
The institutional electronic medical record database (Epic Systems Corp., Madison,
Wisconsin) and endoscopy electronic medical record database (ProVation Medical, Inc.,
Minneapolis, Minn) were queried for all EGDs performed in ICU patients over age 18
for this time period.
Demographic data collected included: gender, age, body mass index (BMI), date and
time of hospital admission, date and time of ICU admission, history of significant
co-existing respiratory disease (i. e. pulmonary fibrosis, chronic obstructive pulmonary
disease, lobectomies, obstructive sleep apnea, asthma, and chronic hypoxemia), any
baseline oxygen requirement, procedure date and duration. Laboratory data included
hemoglobin, hematocrit, international normalized ratio (INR), units of fresh frozen
plasma, packed red blood cells, and platelets transfused prior to the procedure.
Procedural data recorded included: ASA classification, heartrate, oxygen saturation,
blood pressure, and total doses of propofol and fentanyl. Adverse events (AEs) were
defined as hypotension when systolic blood pressure < 90 mmHg, bradycardia when heartrate
< 60 beats per minute (BPM) and oxygen desaturation when pulse oximetry < 90 %. Airway
interventions reviewed included: use of nasopharyngeal or oropharyngeal airway, non-rebreather
mask, bag-mask ventilation, noninvasive ventilation with bi-level positive airway
pressure (BiPAP) or need for endotracheal intubation.
Other procedural data collected included: procedure indication, findings and any endoscopic
interventions that were performed. Lesions were identified as endoscopically treatable
according to American College of Gastroenterology (ACG) gastrointestinal ulcer guidelines
[18]. Esophageal varices with stigmata of recent bleeding such as fibrin clots of red
wale signs were also included as requiring endoscopic treatment. Endoscopic intervention
performed was collected as epinephrine injection, application of hemostatic clips,
bipolar cauterization, and variceal banding. A procedure was also defined as successfully
completed if the second portion of the duodenum (or jejunum in the case of previous
gastric surgery) was reached. The specific reasons for incomplete procedures were
also collected and summarized in [Table 1].
Table 1
EGD Procedural characteristics.
|
Total procedure time in minutes (mean ± SD)
|
15.5 ± 11.0
|
|
Total propofol dose (mg) (mean ± SD)
|
145.9 ± 93.1
|
|
Total fentanyl dose (mcg) (mean ± SD)
|
36.5 ± 22.5
|
|
High-risk lesions (N,%)
|
24 (14.9 %)
|
|
Intervention performed (N,%)
|
17 (70.8 %)
|
|
Successfully completed (N,%)
|
146 (90.6 %)
|
|
Incomplete procedure (N,%)
-
Presence of heme
-
Food in the stomach
-
Obstructive ulcer
-
Obstructive mass
-
Hemodynamic instability
|
7 (4.3 %)
2 (1.2 %)
2 (1.2 %)
2 (1.2 %)
2 (1.2 %)
|
EGD, esophagogastroduodenoscopy; SD, standard deviation
Outcomes
The primary outcome was occurrence of any sedation-related AEs such as hypoxia, bradycardia,
hypotension, or airway intervention as defined above. Secondary outcomes were defined
as successful endoscopic intervention if performed and successful completion of procedure.
Statistical analysis
Descriptive statistics were performed for patient demographic and clinical characteristics.
AEs are reported as proportions of the entire sample. All statistical analyses were
performed using STATA 12.0 (StatCorp LLC, College Station, Texas, United States).
Results
A total of 161 patients’ procedure records out of 239 procedures met inclusion criteria
and had complete data available for extraction during the study period. Patient characteristics
are reported in [Table 2]. Most patients were ASA III (56.5 %). 32.3 % were ASA II, 9.3 % were ASA IV and
only 1.9 % were categorized as ASA I. Average patient age was 60.2 years (± 14.0)
with BMI 27.6 (± 6.5). The average hemoglobin value prior to the procedure was 8.5 g/dL
(± 2.0). A total of 26/161 (16.2 %) had underlying respiratory disease and 104/161
(64.6 %) had baseline requirement of supplemental oxygen. Gastrointestinal bleeding
indications for the procedures were classified as hematemesis 37.2 %, coffee ground
emesis 8.7 %, melena 51.5 %, hematochezia 18.6 %, anemia, 9.9 % or history of ulcer
1.2 %.
Table 2
Patient characteristics.
|
Age (Mean ± SD)
|
60.2 ± 14.0
|
|
BMI (Mean ± SD)
|
27.6 ± 6.5
|
|
Sex (N,%)
|
102 (63.4 %)
59 (36.6 %)
|
|
ASA classification (N,%)
-
ASA I
-
ASA II
-
ASA III
-
ASA IV
|
3 (1.9 %)
52 (32.3 %)
91 (56.5 %)
15 (9.3 %)
|
|
Past medical history of underlying respiratory disease (N,%)
|
26 (16.2 %)
|
|
Patient requiring baseline oxygen (N,%)
|
104 (64.6 %)
|
|
Hemoglobin prior to the procedure (mean ± SD)
|
8.5 ± 2.0
|
|
INR prior to the procedure (mean ± SD)
|
1.6 ± 0.7
|
|
Transfusion history prior to the procedure (mean [min – max] units)
-
PRBC
-
Platelets
-
Fresh frozen plasma
|
1.3 (0 – 17)
0.1 (0 – 4)
0.5 (0 – 8)
|
SD, standard deviation; BMI, body mass index; ASA, American Society of Anesthesiologists;
INR, international normalized ratio; PRBC, packed red blood cells
The primary outcome of sedation-related AEs is summarized in [Table 3]. Only two procedures (1.2 %) were terminated due to sedation-related AEs, one secondary
to hypotension (systolic blood pressure < 80) and the other due to increased requirement
for sedation due to patient’s agitation. On average, oxygen saturation was 97.2 %
(± 3.8 %) with documented desaturation in 12 patients (7.5 %). Interventions to address
sedation-related adverse respiratory events included: use of non-rebreather masks
in eight patients (5.0 %) and use of BiPAP in two patients (1.2 %). No patients required
bag-mask ventilation or endotracheal intubation for mechanical ventilation. No procedures
were terminated due to hypoxia. On average, systolic blood pressure was 104.7 (± 18.2)
mm Hg and diastolic blood pressure 59.8 (± 12.7) mmHg. Average heart rate during procedures
was 86 (± 14.9) BPM. Transient episodes (< 3 minutes) of hypotension (23 %) or bradycardia
(5.0 %) were addressed by delaying the next administered propofol dose.
Table 3
Sedation-related adverse events.
|
Hypoxia
|
97.2 ± 3.8
12 (7.5 %)
|
|
Airway interventions (N, %)
-
Intubation
-
Non-rebreather masks
-
BiPAP[1]
|
0 (0 %)
8 (4.97 %)
2 (1.24 %)
|
|
Hypotension
|
104.7 ± 18.2
59.8 ± 12.7
37 (23.0 %)
|
|
Bradycardia
-
Lowest HR (mean ± SD)
-
< 60 BPM (N,%)
|
86.0 ± 14.9
8 (5.0 %)
|
BiPAP, bilevel positive airway pressure; BP, blood pressure; HR, heart rate; SD, standard
deviation; BPM, beats per minute
1 Required respiratory therapist to administer
Success of endoscopic treatment to achieve hemostasis is summarized in [Table 1]. Twenty-four of 161 procedures (15 %) had lesions identified with high-risk stigmata
of recent bleeding such as: Forrest classification Ia (active spurting), Ib (active
oozing), IIa (visible vessel) and IIb (adherent clot). Successful hemostasis was achieved
in 17 of 24 procedures (70.8 %). Hemostasis was unable to be achieved in the seven
procedures due to findings of mature clot (4 procedures), unable to perform intervention
due to friable mucosa (1 procedure), and difficult location with no active bleeding
(2 procedures).
Successful completion of the procedure was obtained in 146 of 161 procedures (90.6 %).
Thirteen of the 15 (9.3 %) incomplete procedures were due to either presence of food
or blood precluding adequate visualization or obstructive mass or ulcers preventing
further advancement. On average, procedures were 15.5 (± 11.0) minutes long requiring
145.9 mg (± 93.1) of propofol and 36.5 mcg (± 22.5) of fentanyl. Two procedures were
performed using midazolam; one was with propofol and fentanyl and another with midazolam
and fentanyl.
Discussion
EGDs performed in an ICU setting are often performed in patients with significant
comorbidities and increased acuity of illness as reflected in their higher ASA score
[19].These factors place them at higher risk for hemodynamic instability and cardio-respiratory
complications from sedation [20]
[21]. Our study is the first report on the safety and outcomes of NAAP sedation for EGD
in patients admitted to the ICU for management of gastrointestinal bleeding. Our results
suggest that EGDs can be safely and adequately completed with NAAP sedation in patients
admitted to an ICU for gastrointestinal bleeding.
Overall, sedation-related AEs in patients in the ICU undergoing EGD for bleeding who
were sedated via NAAP were uncommon, transient, and rapidly reversed without requiring
termination of the procedure in nearly all patients ([Table 2]). Most cardiovascular events such as hypotension and bradycardia resolved after
increasing the interval between the subsequent propofol administrations per our usual
clinical practice. Desaturations were reversed using interventions such as use of
non-rebreather mask or rarely use of BiPAP. None of the procedures required additional
aid such as bag-mask ventilation or endotracheal intubation. There was no obvious
correlation to the amount of sedation administered to hemodynamic and respiratory
compromise.
There are ample data on safety and efficacy of NAAP sedation when used in outpatient
settings for routine endoscopic procedures [22]
[23]. NAAP sedation has also been found to be safe for advanced interventional endoscopic
procedures including in an elderly population with relatively high comorbidities [24]. Our data support the relative safety and efficacy of NAAP sedation for EGD procedures
in ICU patients. Our institution has a structured training program for propofol administration
when performed by non-anesthesia personnel to ensure endoscopists and nurses are comfortable
with administering sedation and handling sedation-related AEs. A study from Denmark
has also demonstrated the safety of NAPS after undergoing a structured training program
including airway management by both nurses and endoscopists [25].
In 2015 the European Society of Gastrointestinal Endoscopy and the European Society
of Gastroenterology and Endoscopy Nurses and Associates issued an updated guideline
on non-anesthesiologist administration of propofol stating that NAAP can be administered
by personnel who are not involved in the other parts of the procedure and the patient
is continuously monitored. However, the ESGE guidelines further states that in the
presence of risk factors such as ASA ≥ 3, Mallampati class of 3 or conditions increasing
the risk of airway compromise, an anesthesiologist must be present [26]. The 2018 American Society for Gastrointestinal Endoscopy (ASGE) guidelines state
that, “NAPS (nurse administered Propofol sedation) should be administered by personnel
specifically trained in its administration who should have expertise in emergency
airway management and must be present continuously during its use”. It also states
that anesthesia provider – administered sedation be considered for complex endoscopic
procedures or patients with multiple medical comorbidities or at risk for airway compromise
but does not stratify risk by ASA class [27]. Our data demonstrate that NAAP can be safely administered in the ICU setting without
an anesthesiologist to patients with ASA classification ≥ 3 undergoing endoscopy.
Limitations
This study is a retrospective case series and there are limiting factors related to
its retrospective design and lack of a control group. The study design does not allow
us to draw conclusions about dose response or the effect of specific doses on patient
outcomes. Excluding patients on mechanical ventilation and vasopressor support was
important to measure the study outcomes so as not to mask sedation-related AEs. Vital
signs including blood pressure were only charted at 2.5- to 3-minute intervals though
continuous monitoring of oxygen saturation and heart rate was performed. Therefore,
very transient episodes of hypoxemia or bradycardia may have not been recorded. In
addition, a second ICU nurse was present during all procedures solely to chart medications
given and procedural notes, making missing any significant AE recording very unlikely.
Fifteen percent of procedures at our institution identified high-risk lesions; these
lesions can lengthen endoscopy and anesthesia duration (due to need for therapy).
Thus, the results may not be generalizable to institutions with a higher incidence
of high-risk lesions seen on EGD. Finally, this study was performed at a tertiary
care institution where NAAP sedation is the primary method of sedation in both the
ambulatory and ICU setting, thus there is a high level of expertise among endoscopists
performing procedures with NAAP sedation, which may not be applicable in settings
where endoscopists are not experienced with NAAP.
Conclusion
This is the first study describing the safety and efficacy of NAAP sedation for EGD
procedures performed in an ICU. We found that NAAP sedation can be administered safely
and effectively in critically ill patients with a very low incidence of AEs and high
completion rates when the non-anesthesia personnel are adequately trained and experienced.
Larger, prospective, randomized studies in the ICU setting are warranted to compare
NAAP sedation to other forms of sedation for ICU patients undergoing digestive endoscopy.
