Noninvasive continuous monitoring versus intermittent oscillometric measurements for the detection of hypotension during digestive endoscopy.

BACKGROUND: Hemodynamic monitoring during digestive endoscopy is usually minimal and involves intermittent brachial pressure measurements. New continuous noninvasive devices to acquire instantaneous arterial blood pressure may be more sensitive to detect procedural hypotension.
PURPOSE: To compare the ability of noninvasive continuous monitoring with that of intermittent oscillometric measurements to detect hypotension during digestive endoscopy.
METHODS: In this observational prospective study, patients scheduled for gastrointestinal endoscopy and colonoscopy under sedation were monitored using intermittent pressure measurements and a noninvasive continuous technique (ClearSight™, Edwards). Stroke volume was estimated from the arterial pressure waveform. Mean arterial pressure and stroke volume values were recorded at T1 (prior to anesthetic induction), T2 (after anesthetic induction), T3 (gastric insufflation), T4 (end of gastroscopy), T5 (colonic insufflation). Hypotension was defined as mean arterial pressure < 65 mmHg.
RESULTS: Twenty patients (53±17 years) were included. Six patients (30%) had a hypotension detected using intermittent pressure measurements versus twelve patients (60%) using noninvasive continuous monitoring (p = 0.06). Mean arterial pressure decreased during the procedure with respect to T1 (p < 0.05), but the continuous method provided an earlier warning than the intermittent method (T3 vs T4). Nine patients (45%) had at least a 25% reduction in stroke volume, with respect to baseline.
CONCLUSION: Noninvasive continuous monitoring was more sensitive than intermittent measurements to detect hypotension. Estimation of stroke volume revealed profound reductions in systemic flow. Noninvasive continuous monitoring in high-risk patients undergoing digestive endoscopy under sedation could help in detecting hypoperfusion earlier than the usual intermittent blood pressure measurements.

Introduction

Photoplethysmographic techniques combined with volume clamp can provide noninvasive continuous pressure (NICP) monitoring in patients. Although the validation studies have reported conflicting results regarding the interchangeability of these techniques with invasive ones [1-6], several authors consider that discrepancies in measurements should not prevent the physicians to investigate the potential advantages of continuous as opposed to intermittent pressure measurements [7, 8].

Continuous blood pressure monitoring involves arterial catheterization, which is either considered too invasive or simply too cumbersome to be used in some patient populations. Patients undergoing digestive endoscopy for example, are almost never offered an invasive pressure monitoring because the procedure is minimally invasive and its duration is usually short. The number of subjects undergoing combined upper gastrointestinal (GI) endoscopy and colonoscopy is important, since it is one the most frequent interventions performed under anesthesia in Western countries [9]. The current hemodynamic monitoring recommended by the European Society of Anesthesiology for endoscopic procedures includes continuous electrocardiography, pulse oximetry and automated noninvasive intermittent pressure (NIIP) measurements using the oscillometric technique [10]. Arterial pressure values are usually obtained at discrete intervals of five minutes. Hypotension, frequently observed during the procedure, is usually attributed to the vasodilating effect of hypnotic drugs [11-13]. However, gas insufflation used for luminal distension to facilitate gastric and colonic exploration, may potentially impair venous return and impact systemic hemodynamics.

Whether NICP increases the likelihood to detect threatening drops in arterial blood pressure in comparison to NIIP monitoring is not well established. Our primary endpoint was to compare the time-course of mean arterial pressure as obtained using the ClearSight™, a NICP device, with values obtained using NIIP from the anesthesia record sheet of patients undergoing combined upper GI endoscopy and colonoscopy. Our secondary endpoint was to analyze the variations in stroke volume estimated by the ClearSight™ using a pulse contour algorithm, during these procedures.

Materials and methods

Patients

This observational study was performed at a French University hospital. The institutional review board of the French Society of Anesthesiology and Intensive Care Medicine (Comité d’Ethique de la Recherche en Anesthésie-Réanimation) approved the study (IRB 00010254–2016–014). Written informed consent was obtained from all individual participants included in the study before the procedure. Non-consecutive patients undergoing combined upper GI endoscopy and colonoscopy under sedation were prospectively included when investigators and study devices were available. Exclusion criteria were: age under 18, pregnancy, emergency procedure, sepsis, hemodynamic failure, preexisting severe cardiac comorbidity, need for mechanical ventilation, and use of carbon dioxide insufflation for the procedure. This was an exploratory study, and therefore the estimation of the number of subjects to treat was not applicable.

Anesthetic management

Upon arrival in the procedure room, all patients were monitored using a 3-lead electrocardioscope, pulse oximetry and noninvasive intermittent arterial pressure acquired every 5 minutes. In addition, noninvasive continuous arterial pressure measurement was obtained simultaneously using the ClearSight™ monitor (Edwards Lifesciences). The arm-cuff and the digital sensor were placed on the right arm which was the upper arm when the patient was placed in left lateral decubitus for gastric endoscopy. Anesthesia was carried out with a bolus of intravenous propofol (1.5 mg/kg) followed by a continuous infusion (10 mg/kg/hr). If deemed necessary, the anesthesiologist in charge could reduce the infusion rate or titrate additional propofol (0.5 mg/kg boluses) to keep the patient comfortable, while maintaining spontaneous ventilation. No other drug was prescribed for pre-medication or co-sedation. The anesthesiologist was not aware of the noninvasive continuous pressure information, which was collected by an independent investigator. Intraoperative fluid resuscitation was left at the discretion of the anesthesiologist in charge.

Combined gastrointestinal endoscopy and colonoscopy

The patient was positioned in left lateral decubitus for the upper GI endoscopy and then in supine position for the colonoscopy. Expansion of the digestive tract was obtained by air insufflation, using standard settings of the EXERA III Column (Olympus™, Japan). The total volume of air insufflated depended on procedural conditions and physician practice. Complete aspiration of gastric cavity was systematically performed at the end of upper GI exploration and colonic aspiration was achieved during endoscope withdrawal. Air pressure was not monitored routinely during procedures. However, gastroenterologists were asked to provide their subjective appreciation of the amount of air insufflated (major or moderate amount).

Data acquisition

Demographic data including age, gender, height, weight, and ASA class were collected for all patients.

Routine monitoring consisted of intermittent recording of mean, systolic, and diastolic arterial pressure (MAP, SAP, and DAP respectively, mmHg) obtained using the oscillometric technique with a brachial cuff, heart rate (HR, beats/min), and peripheral oxygen saturation (SpO2, %) every ten minutes on the patient’s anesthetic record chart by the anesthetic nurse. The noninvasive continuous monitor acquired and stored beat-by-beat: HR, MAP, SAP, and DAP. In addition, stroke volume (SV, mL) and cardiac output (CO, L/min) were estimated and averaged every 20 seconds. These values were recorded continuously by the noninvasive monitor and analyzed a posteriori by the investigator. For protocol purposes, investigators obtained hemodynamic parameters at five predefined periods: T1, baseline prior to anesthesia; T2, after anesthetic induction; T3, during gastric insufflation; T4, after gastrointestinal endoscopy and prior to colonoscopy; T5, during colonic insufflation.

For each predefined period, noninvasive continuous MAP value was calculated as the average of 5 consecutive cycles and stroke volume was calculated as the average of 5 consecutive values.

Primary and secondary endpoints

The primary end-point of the study was to compare the profiles of MAP over the different time-points as obtained using the noninvasive continuous monitor and the oscillometric technique. The secondary endpoint was to compare the variations of SV over the time-course of the procedure.

Statistical analysis

Data are presented as mean (± standard deviation) or median [interquartile range 25–75] as appropriate for continuous data, and as count (%) for categorical parameters. Comparisons between the independent groups were made using the Chi-squared or Fisher’s exact tests for categorical variables, and using Student t-test or the Mann-Whitney test for quantitative parameters. Repeated measures acquired with intermittent and continuous methods were compared using two-way Analysis of Variance (ANOVA). Normality of data distribution was verified using Kolmigorov-Smirnov test prior to performing ANOVA. Pairwise multiple comparisons were performed using Student-Newman-Keuls method. All reported p values are two-sided, and p values of less than 0.05 were considered to indicate statistical significance. All analyses were performed using SigmaStat® (Jandel Scientific).

Results

From March 2016 to June 2016, 43 patients were prospectively screened. Sixteen patients did not meet the inclusion criteria and 7 were excluded with a final enrollment of 20 patients. The flow of participants through the study is presented in Fig 1.

Fig 1

Flow of participants through the study.

Patient characteristics at baseline and indication for endoscopy are summarized in Table 1. The median duration of the procedure was 34 [15-53] minutes. Gastroenterologists reported that insufflation of a major amount of gas was required for 10 patients (50%), while the others had moderate amounts insufflated.

Table 1

Patients characteristics.

Characteristics	Patients (n = 20)
Age (yr), mean (± SD)	53 (± 17)
Male sex, no. (%)	10 (50%)
Body mass index (kg/m2), mean (± SD)	24 (± 4)
ASA physical status, mean (± SD)	2 (± 0)
Comorbidities
Arterial hypertension, no. (%)	6 (30%)
Diabetes, no. (%)	2 (10%)
Respiratory disease, no. (%)	3 (15%)
Renal disease, no. (%)	4 (20%)
Hepatic disease, no. (%)	3 (15%)
Digestive surgery, no. (%)	3 (15%)
Indications for GI endoscopy
Colorectal cancer, no. (%)	5 (25%)
Anemia, no. (%)	4 (20%)
Abdominal pain, no. (%)	4 (20%)
Gastritis, no. (%)	3 (15%)
Crohn’s disease, no. (%)	2 (10%)
Other, no. (%)	8 (40%)

SD: standard deviation.

Each patient received 5–7 mL/kg of lactated Ringer during the procedure. A single patient required one bolus of IV ephedrine (6 mg) to treat a hypotension episode.

Six patients (30%) had hypotension (MAP < 65 mmHg) detected using standard intermittent oscillometric pressure measurements versus twelve patients (60%) using noninvasive continuous monitoring (p = 0.06). The two-way ANOVA on pressure measurements obtained at the predefined periods revealed a difference between intermittent and continuous methods (p < 0.05). In addition, mean arterial pressure decreased over time compared to baseline (p < 10−5), regardless of the method used for measurement (Fig 2). However, although there was no significant interaction between the NICP and NIIP MAP profiles, the decrease in MAP measured using NICP was detected earlier (T3 vs T1, p < 0.05) than the one obtained using NIIP (T4 vs T1, p < 0.05) (Table 2). The drop in systolic arterial pressure with respect to baseline was more important when assessed with the noninvasive continuous monitoring than with intermittent monitoring (-37 ± -17 mmHg versus -29 ± -17 mmHg, p = 0.03).

Fig 2

Comparison between mean arterial pressure measures by standard (oscillometric) and noninvasive continuous (Clearsight™) monitoring techniques.

Data are presented as box-and-whisker plot with median, quartiles (25%-75%) and percentiles (10th-90th); circles are the data below or above those limits. T1: Prior to anesthetic induction; T2: After anesthetic induction; T3: During gastric insufflation; T4: At the end of the gastroscopy; T5: During colonic insufflation.

Table 2

Hemodynamic values obtained using noninvasive continuous (Clearsight™) and standard (oscillometric) monitoring techniques.

Time-points	T1	T2	T3	T4	T5
Noninvasive continuous monitoring
Stroke volume (mL), median [IQR]	78	64	56	65	64
	[61–86]	[55–83]*	[49–80]* †	[50–77]* ‡	[50–70]* ‡
Systolic arterial pressure (mmHg), median [IQR]	139	121	116	97	87
	[121–163]	[108–144]	[102–130]*	[82–115]* † ‡	[75–94]* † ‡
Mean arterial pressure (mmHg), median [IQR]	95	86	83	74	61
	[87–111]	[81–97]	[76–93]*	[65–81]* † ‡	[57–69]* † ‡
Standard monitoring
Systolic arterial pressure (mmHg), median [IQR]	136	131	115	102	100
	[115–148]	[101–147]	[99–144]	[94–130]*	[87–110]* †
Mean arterial pressure (mmHg), median [IQR]	100	97	91	79	74
	[86–113]	[79–104]	[74–107]	[70–95]*	[66–78]* † ‡
Heart rate (bpm), median [IQR]	80 [65–92]	80 [72–91]	83 [75–94]	80 [68–88]	75 [68–80]
Saturation of peripheral oxygen (%), median [IQR]	99 [98–100]	99 [97–100]	99 [96–100]	98 [96–100]	99 [97–100]

IQR: Interquartile range. T1: Prior to anesthetic induction; T2: After anesthetic induction; T3: During gastric insufflation; T4: At the end of the gastroscopy; T5: During colonic insufflation.

* p < 0, 01 vs T1,

† p < 0.01 vs T2,

‡ p < 0.01 vs T3.

There were more hypotensive episodes detected when the gastroenterologist declared using major gas insufflation (90%) than when the insufflation was moderate (30%) (p = 0.02) (Fig 3).

Fig 3

Comparison of the rate of arterial hypotension measured by noninvasive continuous monitoring between moderate and major insufflation.

There was a marked reduction in stroke volume during gastric insufflation (56 [26-86] mL), both when compared to baseline (78 [53-103] mL; p < 0.01) and after anesthesia induction (64 [36-92] mL; p < 0.01) (Fig 4). Stroke volume was also significantly lower following anesthesia induction (T2) when compared with baseline (T1) (p < 0.01). No significant difference was detected in stroke volume before and after colonic insufflation (Table 2). Nine of the 20 patients (45%) had a 25% reduction or more in stroke volume during the procedure, with respect to baseline.

Fig 4

Stroke volume (SV) evolution during endoscopy using noninvasive continuous monitoring.

Data are presented as box-and-whisker plot with median, quartiles (25%-75%) and percentiles (10th-90th); circles are the data below or above those limits. T1: Prior to anesthetic induction; T2: After anesthetic induction; T3: During gastric insufflation; T4: At the end of the gastroscopy; T5: During colonic insufflation.

Discussion

In this cohort of spontaneously breathing patients, mean arterial pressure decreased significantly at the end of GI endoscopy and during colonoscopy. These variations were more pronounced according to noninvasive continuous monitoring (ClearSight™, Edwards) in comparison to intermittent oscillometric pressure measurements. Stroke volume also diminished during the procedure under propofol sedation, especially during gastric insufflation.

Hypotension during endoscopy is described as a recurrent complication reported in 5 to 32.5% of patients [14, 15]. In our cohort, 30% of the patients experienced hypotension (MAP < 65 mmHg) according to standard intermittent monitoring, but this figure increased to 60% according to noninvasive continuous monitoring. Oscillometric pressure measurement using an arm-cuff is the current recommended method to quantify arterial pressure during this procedure [10]. However, our observations confirm that the MAP variations were more frequent and more profound when the NICP was considered instead of standard NIIP. This result corroborates a previous study in patients undergoing digestive endoscopy that demonstrated a greater sensitivity of noninvasive continuous measurements for the detection of arterial pressure variations [16].

Arterial hypotension detected during upper and lower GI endoscopy appears to be multifactorial. Decreased arterial pressure is usually attributed to the vasodilating effect of sedative agents [11, 12]. Propofol is known to induce arteriolar vasodilatation [13] with a subsequent decrease in systemic vascular resistance, which in turn reduces mean arterial pressure. There is no guideline describing the “ideal” sedation technique during digestive endoscopy. We used a standard anesthesia protocol during the study to minimize the variations in arterial pressure resulting from differences in sedation regimen between patients. A bolus followed by a continuous infusion of intravenous propofol allowed for a suitable sedation during the whole procedure with minimum requirements for individual adjustments. Our observation supports the hypothesis that digestive gas insufflation impairs venous return, reduces stroke volume and could have its own role in the observed hypotension. There were, indeed, more hypotension episodes when the gas insufflation was estimated as “major” according to the operator. Stroke volume decreased after gastro-intestinal insufflation compared to anesthetic induction. This could be related to increased intra-abdominal pressure after air insufflation, which caused decreased venous return, stroke volume reduction, and further hypotension.

The clinical impact of such transient arterial pressure decrease remains uncertain. In this small exploratory study, we did not look at post-procedural morbidity. However, it is now well established that intraoperative arterial hypotension is an independent predictor of increased one-year mortality, especially in patients with pre-existing comorbidities [17-19]. We can only suspect that excess hypotension might be deleterious in patients with cardiovascular comorbidities undergoing gastro-intestinal endoscopy, but further investigation is warranted to explore this hypothesis.

This study has some limitations. First, our design is observational and descriptive, thus no causal relation between hemodynamic variations and the procedure can be inferred. Second, the ClearSight™ monitor has been compared to different current invasive devices for cardiac output measurements [8, 20–22] with acceptable reliability but this monitoring technique cannot be considered as clinically interchangeable with other measures of stroke volume [1]. Third, patient inclusion was not consecutive and was limited by investigator availability; however, our population was representative of patients undergoing endoscopy in our hospital. Finally, despite the small size of the cohort studied, we were able to detect a large difference in the detection of hypotension according to the method used for pressure monitoring.

Conclusion

We observed that noninvasive continuous monitoring was more sensitive than intermittent oscillometric pressure measurements to detect hypotension during digestive endoscopy under sedation. Profound reductions in stroke volume could be inferred from the noninvasive arterial pressure waveforms. Similar hemodynamic alterations during surgical procedures under general anesthesia would normally prompt therapeutic interventions to improve the determinants of tissue perfusion. Although we have no data to support an increased risk of complications in our population, the current understanding is that there might be a benefit in correcting such hemodynamic alterations. We suggest that noninvasive continuous monitoring of arterial pressure and stroke volume should be used to detect relevant hemodynamic alterations in high-risk patients undergoing digestive endoscopy under sedation. A large prospective randomized trial investigating the potential benefit of treating these alterations on the outcome of this population is desirable.

Strobe statement.

(DOCX)

Click here for additional data file.

17 Aug 2020

PONE-D-20-21784

Noninvasive continuous monitoring versus intermittent oscillometric measurements for the detection of hypotension during digestive endoscopy.

PLOS ONE

Dear Dr. Anh-Dao Phan

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

I would appreciate if pay careful attention in revising your manuscript  according to the reviewer comments.

Please submit your revised manuscript by Oct 01 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Ehab Farag, MD FRCA FASA

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for stating the following in the Source of funding Section of your manuscript:

"Edwards Laboratories provided the ClearSightTM sensors free of charge, but Edwards had no role in designing the study, collecting or analyzing the data, writing the manuscript or participating in the decision to submit it for publication."

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

"The authors received no specific funding for this work."

Additionally, because some of your funding information pertains to commercial funding, we ask you to provide an updated Competing Interests statement, declaring all sources of commercial funding.

In your Competing Interests statement, please confirm that your commercial funding does not alter your adherence to PLOS ONE Editorial policies and criteria by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” as detailed online in our guide for authors  http://journals.plos.org/plosone/s/competing-interests.  If this statement is not true and your adherence to PLOS policies on sharing data and materials is altered, please explain how.

Please include the updated Competing Interests Statement and Funding Statement in your cover letter. We will change the online submission form on your behalf.

3. Thank you for stating the following in the Competing Interests section:

"I have read the journal's policy and the authors of this manuscript have the following competing interests: Bernard Cholley has participated to advisory boards organized by Edwards Lifesciences."

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Interesting paper, but should be deeply corrected.

Abstract: it is confusing and not clear.

Methods.

Due to reduced sample size, check for normality should be performed.

Sample size calculation should be added

It is not clear if patients included were consecutive or not

Variations due to operators should be added

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Fabrizio D'Ascenzo

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

3 Sep 2020

Point-by-point responses to the editor and the reviewer

Dear Editor, dear Reviewer

We thank you for your thankful appreciation and this careful reviewing which has enabled us to greatly improve the quality of our manuscript entitled “Noninvasive continuous monitoring versus intermittent oscillometric measurements for the detection of hypotension during digestive endoscopy ”.

At your and the reviewer’s request, we in this letter diligently address every point that you have asked us to improve. Changes in the revised version of the manuscript are highlighted in red.

Responses to Editor

1. Please ensure that your manuscript meets PLOS ONE's style requirements

Answer: We have made the necessary changes to our manuscript in order to meet PlosOne Requirements

2. Funding statement and competing interests

Answer: We have modified funding and competing statement according to the requirements. Modified funding and competing interest statements have been included in the new cover letter.

3. Competing interest section

Answer: The statement has been modified as required and indicated in the new cover letter.

4. Supporting Information

Answer: We have modified the supporting information following your instruction.

Responses to Reviewer

1. Abstract unclear

Answer: We have revised thoroughly the abstract to clarify the message. We have also removed abbreviations as recommended. The revised abstract length is 251 words.

2. Normality check.

Answer: The normality of the data distribution (SAP, MAP, SV) was verified using Kolmogorov-Smirnov test (SigmaStat®). This precision has been added to the manuscript (page 7, lines 156-157).

3. Sample size calculation

Answer: This was an exploratory study. Prior to its completion, we had no idea of the difference of sensitivity between continuous and intermittent pressure measurements in the detection of hypotension. Therefore, we could not estimate a sample size prospectively. This was explained in the method section (page 5, line 93-95).

4. Non-consecutive patients

Answer: Patients could be enrolled in the study only when, both, investigators and equipment were available. Therefore, the patients included in this study were not consecutive. This precision has been added in the manuscript (page 4, lines 88-90)

5. Inter-operator variability

Answer: All patients were anesthetized according to our institution protocol and received similar anesthetic drugs and beseline fluid infusion. In case of hypotension, the physician in charge was free to decide to reduce the propofol infusion rate or to inject a bolus of ephedrine. Most anesthesiologists choose to modify propofol and a single patient has received a bolus of ephedrine. This is indicated page 9, line 179.

Regarding the endoscopic management, the inter-operator variability was mainly related to the amount of gas insufflated. Since it was not possible to quantify this parameter, we choose to collect the estimation of the endoscopist regarding his subjective appreciation of the amount of gas insufflated. This was the best we could achieve in order to provide information regarding this important aspect of the procedure since (as suggested by our results) it could greatly influence systemic hemodynamics (see Figure 4).

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

23 Sep 2020

Noninvasive continuous monitoring versus intermittent oscillometric measurements for the detection of hypotension during digestive endoscopy.

PONE-D-20-21784R1

Dear Dr.

Anh-Dao Phan

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Ehab Farag, MD FRCA FASA

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

25 Sep 2020

PONE-D-20-21784R1

Noninvasive continuous monitoring versus intermittent oscillometric measurements for the detection of hypotension during digestive endoscopy

Dear Dr. Phan:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Ehab Farag

Academic Editor

PLOS ONE