Hypotension Prediction Index to Predict Epidural-labor Analgesia Induced Hypotension -- Pilot Study
Phase: NA
Conditions: Anesthesia, Epidural, Hypotension
Sponsor: Grace Lim, MD, MS

Title: 
Hypotension prediction index to predict epidural-labor analgesia induced 
hypotension—PILOT 
IRB ID: STUDY23030009 
 
Investigators: Grace Lim MD, MS; Alexandra Nicholas MD; Andrea Ibarra MD, MS; Patricia 
Dalby MD; Christopher Tyler Smith MD 
NCT: NCT05906368 
 
Affiliation: 
Department of Anesthesiology and Perioperative Medicine 
University of Pittsburgh School of Medicine 
Institution: 
University of Pittsburgh/UPMC 
 
 
Document Date: 07 AUG 2024 

Research Protocol Form 
 
Title: 
Hypotension prediction index to predict epidural-labor analgesia induced hypotension—PILOT 
 
Investigators: Grace Lim MD, MS; Alexandra Nicholas MD; Andrea Ibarra MD, MS; Patricia Dalby MD; 
Christopher Tyler Smith MD 
Affiliation: 
Department of Anesthesiology and Perioperative Medicine 
University of Pittsburgh School of Medicine 
 
Institution: 
University of Pittsburgh/UPMC 
 
 
I. Research Objectives and Purpose 
 
1. 
Research Key Questions(s): Can hypotension prediction index (HPI, ClearSight, Edwards 
Lifesciences, Irvine, USA) reduce time-to-treatment of epidural labor analgesia (ELA)-associated 
hypotension? 
2. 
Hypotheses: HPI will have clinically significant reductions in time-to-treatment of ELA-associated 
hypotension compared to conventional non-invasive blood pressure monitoring methods. 
 
II. Research Significance 
1. Background: 
Despite decades of safe use, hypotension after epidural labor analgesia (ELA) remains the most common 
complication, experienced by an average of 1 of every 5 patients receiving ELA. Hypotension has safety 
ramifications to both mother and fetus and results in, at its mildest, maternal lightheadedness and nausea, 
and at its most severe, fetal acidemia and difficulties with fetal-to-neonatal transition. These safety concerns 
make early detection, prevention, and treatment of ELA-associated hypotension a critical component of 
safety on labor & delivery units worldwide. 
Currently, conventional monitoring involves intermittent non-invasive blood pressure checks to detect and 
treat hypotension. The current American Society of Anesthesiologists Guidelines on Obstetric Anesthesia 
Practice1 recommend monitoring for hypotension, with most practices using non-invasive cuff measures, 
typically expected every 5-15 minutes. However, intermittent monitoring potentially results in delays in 
recognition and treatment of low blood pressure2. Delays in treating epidural anesthesia-associated 
hypotension can result in inadequate maternal-fetal perfusion3. Further, causes of hypotension after 
neuraxial in obstetric patients are primarily driven by reductions in systemic vascular resistance4 (SVR). 
Early detection of ELA-associated hypotension is critically needed to facilitate earlier treatments with 
vasopressors, typically consisting of either ephedrine or phenylephrine. 
Our proposed solution involves using the hypotension prediction index (HPI, ClearSight, Edwards 
Lifesciences, Irvine, USA) to reduce time-to-treatment of epidural labor analgesia (ELA)-associated 
hypotension. The HPI algorithm on ClearSight uses arterial waveform features to predict hypotension, 
defined by mean arterial pressure (MAP) < 65 mmHg for at least 1 minute5. The index ranges 0 to 100 with 
higher numbers reflecting a higher likelihood of subsequent hypotension. HPI has 92% sensitivity and 
specificity for predicting hypotension 5 min in advance, sensitivity 89% and specificity 90% for 10 min in 
advance and 88% and 87% for 15 min in advance6. The sensitivity and specificity of HPI to accurately 
predict hypotension has also been validated with conventional invasive and non-invasive arterial waveforms, 
in both pregnant and non-pregnant cohorts.7 8 9 10 11 12 Other studies have similarly demonstrated the 
effectiveness of HPI in predicting hypotension in perioperative settings.13 14 15 The algorithm is approved for 
sale in Europe and the United States. To our knowledge, no study to date has rigorously assessed the utility 
of HPI in ELA compared to conventional monitoring, for the benefits of reduced time-to-treatment of ELA- 
associated hypotension. 
This trial will investigate the ease of use and feasibility of the ClearSight monitoring system in comparison to 
the Conventional blood pressure monitor (upper arm cuff) during and after epidural-labor analgesia 
 
 
 
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placement. The pilot study will compare time-to-treatment of hypotension between conventionally monitored 
patients (Group CM) and those receiving HPI (Group HPI) monitoring by ClearSight, in a population of 
healthy people receiving ELA, and with the intent to expand this pilot study to a larger population of women 
to meet the power required to identify difference in time to treatment for hypotensive events. 
2. Significance/Rationale: 
This research question is significant because identifying patients at risk for ELA-associated hypotension 
will reduce the risk for the most common complication of ELA, hypotension. Earlier treatment of 
hypotension will improve safety and patient experience, by reducing maternal side effects (nausea, 
vomiting, lightheadedness) and fetal-neonatal risks (acid-base disturbances, neonatal transition 
challenges). It has the potential to change practice by facilitating clinical team performance to make earlier 
recognition, prophylaxis, and treatment decisions for the hundreds of thousands of patients receiving ELA 
annually. 
 
III. Investigational Plan 
 
1. Study design: 
Prospective randomized controlled trial 
 
2. Methods: 
a. Size of study groups(s): The primary outcomes are 1.) ease and feasibility of use of the ClearSight 
monitoring system during labor and delivery, post-epidural-labor analgesia placement; and 2.) time-to- 
treatment of hypotension, defined as MAP <65 mmHg for more than 1 minute. Our initial pilot sample is 
expected to identify the ability to use the ClearSight monitoring in the labor and delivery suite, the 
patient adherence to the finger cuff monitors, and the feasibility of hypotension detection at the central 
monitors. The pilot sample (N = 30) is not expected to demonstrate significant differences in the relation 
between mode of blood pressure measurement and time-to-treatment of hypotension but should yield 
an estimate of the potential differences for a continuance of study. 
 
b. Environment and Estimated timeline to sample size acquisition: UPMC Magee performs about 
7,400 ELA annually, a range of 20-30 ELA daily. Based on a meta-analysis of trials, the estimated 
incidence of hypotension after initiation of neuraxial analgesia during labor is approximately 19% 
(range: 3-35%).16 Our internal data that shows approximately 20-30% of patients receiving ELA require 
treatment with a vasopressor within the first 4 hours of ELA initiation; we will use the conservative 
estimate of 20%. Our internal experience with similar trials also informs our timeline: in our prior 
experiences with similar labor and delivery trials we have achieved a consistent approach-to-recruit 
ratio of about 25%. Based on our volume, ELA utilization, eligibility criteria, and rates of ELA-associated 
hypotension, we estimate a total of 5-8 weeks of recruitment. A total of N=30 patients will be enrolled 
with a predicted 20% (n=6) experiencing hypotension events of interest. 
c. Outcomes: 
Primary outcome: 
Ease of use of ClearSight blood pressure monitoring system 
(0 – 10) Ratings from patient and patients’ assigned nurse during ELA 
Feasibility of blood pressure monitoring (yes/no response from assigned nurse regarding 
patient care. 
Time-to-treatment of hypotension (minutes) 
 
Secondary outcomes: (only exploratory) 
Total time in hypotension with MAP <65 mmHg 
Nausea 
Vomiting 
Total phenylephrine, mg 
Total ephedrine, mg 

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Total intravenous fluids, mL 
Changes in fetal heart rate category 
Presence or absence of fetal heart rate decelerations within 1 hour of initiation of ELA 
CO, CI, SV, SVV 
d. Patient inclusion, exclusion, and withdrawal criteria: 
Inclusion 
Pregnant 
Receiving epidural labor analgesia (ELA) 
 
Exclusion 
Non-reassuring fetal tracing at the time of ELA request 
Contraindications to ELA 
Significant cardiac arrhythmias or aortic regurgitation 
Arrhythmia 
Treatment with antihypertensive medications 
Pre-eclampsia with or without severe features 
Preoperative infection 
Inability to use ClearSight device for any reason. 
Incomplete data 
Sustains unintentional dural puncture during ELA placement 
 
e. Protocol specific methods: 
Patients will be screened electronically using the electronic health record upon arrival at the 
Womancare birth center at UPMC Magee. Patients are eligible if they are pregnant, admitted for labor 
and delivery, and receiving ELA. If patients are undecided about whether they will receive ELA but are 
interested in the research, they may be consented and then marked as a “screen failure” if they do not 
receive ELA. These patients will not be randomized. Patients who receive ELA will be randomized to 
treatment of hypotension according to conventional monitoring (Group CM) or monitoring by HPI 
(Group HPI). Randomization will be 1:1 and occurs immediately after informed consent and signature 
for research activities. Subjects will be informed of their assignment after all research activities and data 
collection have been completed."Total monitoring time will be 4 hours starting from the initiation of ELA. 
To enable group comparisons of total time in hypotension, all participants will wear ClearSight and a 
Conventional Monitoring cuff; Group CM will be blinded to ClearSight output and receive standard care 
for the treatment of hypotensive events post-epidural-labor analgesia. Group HPI will receive treatment 
of hypotension according to ClearSight output and specified by the hypotension treatment protocol 
below. 
Clinical research staff who have been trained in ClearSight will apply the device and troubleshoot any 
problems. Providers will be trained on the monitor, its interpretation, and output, prior to study launch 
and real time at the time of active study participant enrollment. This training applies only to those 
participants who will receive non-blinded treatment assignment 
Pre-ELA Protocol 
Participants will receive 500mL crystalloid co-load to be started and administered during placement of 
ELA. Because pregnant women in lateral decubitus positions can result in 10mmHg differences in 
dependent and upper arm blood pressures, the anticipated initial post-ELA decubitus position of the 
patient will be clarified as Right or Left lateral decubitus; standard monitoring will be applied including 
pulse oximeter and non-invasive blood pressure (NIBP) cuff affixed over the patient’s arm anticipated to 
be in the upper (not dependent) position. In Group HPI both ClearSight and NIBP monitors will be 
applied on the same arm. 

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ELA Protocol: Combined Spinal Epidural (CSE) Analgesia 
A baseline blood pressure will be recorded immediately prior to the initiation of ELA. 
At patient request, an experienced anesthesia provider will perform procedure to place ELA using CSE 
technique in the sitting position. CSE is chosen due to reliability and rapidity with which hypotension 
can be predicted within the ELA encounter. A meta-analysis of studies comparing low-dose epidural 
analgesia with CSE analgesia found no difference in the incidence of hypotension between the two 
techniques. 
The epidural space will be found using loss of resistance to saline. A 25-27g Sprotte needle will be 
introduced to the subarachnoid space. After confirmation of cerebrospinal fluid (CSF), a spinal dose of 
15mcg fentanyl and 2.5mg bupivacaine will be given (this action defines T0 = initiation of CSE). At T0 
blood pressure monitoring and data recordings will begin per protocol specified below. 
A 19-20g flexible epidural catheter will then be introduced and threaded 5-6cm in the epidural space. 
Test dose will be delivered through the epidural catheter and will consist of lidocaine 1.5% with 
epinephrine, 3mL. The anesthesia clinician will declare positive or negative test dose 5 min after 
administration of test dose. A positive test dose will result in withdrawal from the study. 
Maintenance of ELA will be by patient-controlled epidural analgesia using programmed intermittent 
epidural bolus (PIEB) at our institutional standards: Ropivacaine 0.1% +2mcg/mL fentanyl, 8mL 
q40min, 8mL demand q8min, maximum hourly volume 24mL. (Smiths CADD®-Solis Infusion System, 
Infusion Pump, ICU Medical, Dublin, OH). The first PIEB dose is delivered 40 minutes after the initiation 
of the pump. 
Hypotensive Event Measurement: 
Hypotension Definition: MAP <65 mmHg for more than 1 minute. In Group CM, hypotension will be 
measured by conventional non-invasive blood pressure cuff. In Group HPI hypotension will be 
measured by ClearSight. 
In typical clinical ELA settings, the following definition for hypotension is used to guide BP treatment: 
drop in systolic blood pressure (SBP) >20% from baseline, or systolic blood pressure <100 mmHg, or, if 
there are any fetal heart rate concerns. These parameters will continue per existing clinical standards 
and are expected to be evenly randomly distributed between the two groups by virtue of randomization. 
The Group HPI treatment protocol adds to the Conventional monitoring protocol as the ClearSight 
monitor and monitoring algorithm more clearly delineate types of hypotensive events. 
In Group HPI we used an index threshold for treatment that builds upon findings from Maheshwari et 
al.17 In their pilot randomized trial of 214 noncardiac surgical patients, 105 (49%) patients randomized 
to management with a hypotension prediction algorithm, intraoperative hypotension was not reduced 
compared with controls. They suggested that a lower alert threshold enabling adequate warning time, 
and a simpler treatment algorithm that emphasizes prompt treatment after alert may help. Therefore, 
our HPI alert threshold for treatment is specified at 75 (on the monitor/ClearSight algorithm) and the 
treatment algorithm, specified below, was made as simple as possible. 
 
 
Blood Pressure Monitoring and Hypotension treatment protocol is standardized as below. 
 
BP MONITORING PROTOCOL 
 
Group CM 
Group HPI 

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T0 At the time of test dose delivery, automated 
NIBP cycles will begin q3min for 30 
minutes, amounting to a total of at least 10 
blood pressure measurements. 
T30 After 30 minutes, NIBP cycles to q15min per 
existing clinical standards 
T4hours Monitoring for research ends 
T0 
At the time of test dose delivery, Clearsight 
monitoring continues. 
T0 – T4hours ClearSight monitoring is continuous 
T4hours Monitoring for research ends 
 
 
HYPOTENSION** TREATMENT PROTOCOL 
 
Group CM 
Group HPI 
First hypotensive episode: 
• 
500mL IV bolus 
• 
Ephedrine 10mg IVP (unless otherwise 
specified by physician anesthesiologist of 
record) 
Second hypotensive episode: 
• 
Ephedrine 10mg IVP (unless otherwise 
specified by physician anesthesiologist of 
record) 
Third hypotensive episode: 
• 
Physician anesthesiologist of record 
discretion 
First HPI alert /First hypotensive episode: 
• 
Look at hemodynamic relations screen 
• 
If it is a preload issue, give 500mL IV 
bolus 
• 
If it is a contractility or afterload issue, 
give Ephedrine 10mg IVP (unless 
otherwise specified by physician 
anesthesiologist of record) 
Second HPI alert /Second hypotensive episode: 
• 
Look at hemodynamic relations screen 
• 
If it is a preload issue, give 500mL IV 
bolus 
• 
If it is a contractility or afterload issue, 
give Ephedrine 10mg IVP (unless 
otherwise specified by physician 
anesthesiologist of record) 
Third HPI alert /Third hypotensive episode: 
• 
Physician anesthesiologist of record 
discretion 
**Hypotension as defined above 
Key: MAP: mean arterial pressure; CM: conventional monitoring (standard care); HPI: hypotensive prediction 
index group (ClearSight device and algorithm); BP: blood pressure; SBP: systolic blood pressure; NIBP: 
non-invasive blood pressure; IVP: Intravenous push 

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e. Electronic Health Record Variables Collected: 
• 
Age 
• 
Race/Ethnicity 
• 
Insurance status 
• 
Gravidity 
• 
Parity 
• 
Estimated gestational age 
• 
Body mass index 
• 
Induction vs Spontaneous Labor 
• 
Last known cervical exam at the time of ELA initiation 
• 
Pain score immediately prior to ELA initiation 
• 
Total vasopressor doses from time of ELA initiation until delivery 
• 
Time of hypotensive event start to time of treatment for hypotension 
• 
Changes in fetal heart rate Yes/No 
o If Yes: Time, in minutes, from ELA initiation until category change detected 
• 
Presence or absence of fetal heart rate decelerations within 1 hour of initiation of ELA (yes/no) 
• 
Mode of delivery 
• 
Neonatal weight 
• 
Neonatal Apgar scores 
• 
Neonatal cord blood pH 
3. Risks/Benefits: 
Benefits 
Close monitoring and treatment of hypotension 
Risks 
Loss of confidentiality 
Discomfort with devices 
Inconvenience answering questions 
Risk of obtaining a false positive reading and being given fluids or other management of blood pressure 
that was not necessary. 
 
4. Data Analysis: 
a. Data collection form: See Appendix 
b. Statistical Analysis Plan 
Descriptive statistics will be calculated for variables and compared between groups. We will report mean ± 
SD for normally distributed continuous data; median (interquartile range) for data not normally distributed or 
for data with outliers or ordinal data; and number (percentage) for categorical data. Kolmogorov–Smirnov 
test will be applied to test for normality of data distribution. An unpaired two-tailed t test will be used for 
comparing parametric data between groups, and Mann–Whitney U and Wilcoxon rank sum tests will be 
used for nonparametric data. The chi-square test or Fisher exact test will be applied as appropriate for 
comparing proportions between groups. P < 0.05 will be considered statistically significant. 
 
Primary Outcome Analysis (Survival Analysis) 
Single-variable proportional hazards regression models will be created for each potential covariate of 
interest. Time-to-event estimates +/-SE for both groups will be calculated from the single-variable models. 
Using P < 0.10 from the univariate models as a threshold for inclusion in the multivariable model, the best- 
fit multivariable model will then be generated by removing variables with P > 0.05 from the multivariable 
model in a backward stepwise fashion. To assess the primary outcome regarding relationship between 
treatment groups and “survival” (treatment-free) time, a proportional hazards model will be used to assess 
the effect of the monitoring type, with effects of covariables controlled in the best-fit multivariable model. 

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Secondary Outcome Analyses 
The secondary outcomes that will be compared between groups will include total time in hypotension, 
nausea, vomiting, total phenylephrine and ephedrine (mg) doses, total intravenous fluids in labor (mL), 
changes in fetal heart rate category, presence, or absence of fetal rate decelerations within one hour of 
initiation of ELA, and hemodynamic variables (CO, CI, SV, SVV). We will report mean ± SD for normally 
distributed continuous data; median (interquartile range) for data not normally distributed or for data with 
outliers or ordinal data; and number (percentage) for categorical data. Kolmogorov–Smirnov test will be 
applied to test for normality of data distribution. An unpaired two-tailed t test will be used for comparing 
parametric data between groups, and Mann–Whitney U and Wilcoxon rank sum tests will be used for 
nonparametric data. The chi-square test or Fisher exact test will be applied as appropriate for comparing 
proportions between groups. P < 0.05 will be considered statistically significant. 
In Group HPI, we will use mediation and moderation analyses to assess the ELAHypotension association 
explained by hemodynamic parameters: Cardiac Output (CO), Stroke Volume (SV), Stroke Volume 
Variation (SVV), Systemic Vascular Resistance (SVR). 
 
 
APPENDIX. 
Data Collection Forms. 

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REFERENCES 
 
1 Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of Anesthesiologists Task 
Force on Obstetric Anesthesia and the Society for Obstetric Anesthesia and Perinatology. Anesthesiology. 2016 
Feb;124(2):270-300. doi: 10.1097/ALN.0000000000000935. PMID: 26580836. 
2 Zheng X, Siddiqui Z, Anderson N, Chen CM, Chatterji M, Smiley R, Landau R, Meng ML. Check the Blood Pressure!: An 
Educational Tool for Anesthesiology Trainees Converting Epidural Labor Analgesia to Cesarean Delivery Anesthesia. A A 
Pract. 2020 Apr;14(6):e01174. doi: 10.1213/XAA.0000000000001174. PMID: 32132359. 
 
3 Zheng et al 
4 Dyer RA, Reed AR, van Dyk D, et. al.: Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of 
phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology 2009; 111: pp. 753- 
765. 
 
5 Hatib F, Jian Z, Buddi S, Lee C, Settels J, Sibert K, Rinehart J, Cannesson M: Machine-learning algorithm to predict 
hypotension based on high-fidelity arterial pressure waveform analysis. Anesthesiology. 2018; 129:663–74. 
6 Hatib F, Jian Z, Buddi S, Lee C, Settels J, Sibert K, Rinehart J, Cannesson M: Machine-learning algorithm to predict 
hypotension based on high-fidelity arterial pressure waveform analysis. Anesthesiology. 2018; 129:663–74. 
 
7 Frassanito, L., Giuri, P.P., Vassalli, F. et al. Hypotension Prediction Index with non-invasive continuous arterial pressure 
waveforms (ClearSight): clinical performance in Gynaecologic Oncologic Surgery. J Clin Monit Comput 36, 1325–1332 
(2022). 
 
8 Hatib F, Jian Z, Buddi S, Lee C, Settels J, Sibert K, Rinehart J, Cannesson M: Machine-learning algorithm to predict 
hypotension based on high-fidelity arterial pressure waveform analysis. Anesthesiology. 2018; 129:663–74. 
9 Maheshwari, K., Buddi, S., Jian, Z. et al. Performance of the Hypotension Prediction Index with non-invasive arterial 
pressure waveforms in non-cardiac surgical patients. J Clin Monit Comput 35, 71–78 (2021). 
 
10 The Use of Non-Invasive Continuous Blood Pressure Measuring (ClearSight®) during Central Neuraxial Anaesthesia 
for Caesarean Section-A Retrospective Validation Study. Helmer P, Helf D, Sammeth M, Winkler B, Hottenrott S, 
Meybohm P, Kranke P. J Clin Med. 2022 Aug 2;11(15):4498. doi: 10.3390/jcm11154498. PMID: 35956113. 
11 Impact of non-invasive continuous blood pressure monitoring on maternal hypotension during cesarean delivery: a 
randomized-controlled study. Juri T, Suehiro K, Kimura A, Mukai A, Tanaka K, Yamada T, Mori T, Nishikawa K. J Anesth. 
2018 Dec;32(6):822-830. doi: 10.1007/s00540-018-2560-2. Epub 2018 Sep 28. PMID: 30267340. 
12 Frassanito L, Sonnino C, Piersanti A, Zanfini BA, Catarci S, Giuri PP, Scorzoni M, Gonnella GL, Antonelli M, Draisci G. 
Performance of the Hypotension Prediction Index With Noninvasive Arterial Pressure Waveforms in Awake Cesarean 
Delivery Patients Under Spinal Anesthesia. Anesth Analg. 2022 Mar 1;134(3):633-643. doi: 
10.1213/ANE.0000000000005754. PMID: 34591796. 
 
13 Prediction and Prevention of Intraoperative Hypotension with the Hypotension Prediction Index: A Narrative Review. 
Sidiropoulou T, Tsoumpa M, Griva P, Galarioti V, Matsota P. J Clin Med. 2022 Sep 22;11(19):5551. doi: 
10.3390/jcm11195551. PMID: 36233419. 
 
14 Ability of an Arterial Waveform Analysis-Derived Hypotension Prediction Index to Predict Future Hypotensive Events in 
Surgical Patients. Davies SJ, Vistisen ST, Jian Z, Hatib F, Scheeren TWL. Anesth Analg. 2020 Feb;130(2):352-359. doi: 
10.1213/ANE.0000000000004121. PMID: 30896602. 
15 Effective hemodynamic monitoring. Pinsky MR, Cecconi M, Chew MS, De Backer D, Douglas I, Edwards M, Hamzaoui 
O, Hernandez G, Martin G, Monnet X, Saugel B, Scheeren TWL, Teboul JL, Vincent JL. Crit Care. 2022 Sep 
28;26(1):294. doi: 10.1186/s13054-022-04173-z. PMID: 36171594. 

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16 Simmons SW, Taghizadeh N, Dennis AT, et. al.: Combined spinal-epidural versus epidural analgesia in labour. 
Cochrane Database Syst Rev 2012; CD003401. 
17 Maheshwari K, Shimada T, Yang D, Khanna S, Cywinski JB, Irefin SA, Ayad S, Turan A, Ruetzler K, Qiu Y, Saha P, 
Mascha EJ, Sessler DI. Hypotension Prediction Index for Prevention of Hypotension during Moderate- to High-risk 
Noncardiac Surgery. Anesthesiology. 2020 Dec 1;133(6):1214-1222. doi: 10.1097/ALN.0000000000003557. PMID: 
32960954