Anesthesia for Upper Endoscopy and Colonoscopy in Cardiac Patients With Acute Anemia

• ClinicalTrials.gov Identifier: NCT04857450
• Recruitment Status: Recruiting
• First Posted: April 23, 2021
• Last Update Posted: April 23, 2021
• Sponsor: King Saud University
• Information provided by (Responsible Party): Mostafa Mohammed Elsaid Elhamamsy, King Saud University

Tracking Information

• First Submitted Date: April 20, 2021
• First Posted Date: April 23, 2021
• Last Update Posted Date: April 23, 2021
• Actual Study Start Date: November 20, 2020
• Estimated Primary Completion Date: November 20, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 20, 2021)

Measurement of serum cortisl level [ Time Frame: From preoperative baseline to post operative after 6 hours ]

Primary goal was to prove that if we combined etomidate with small dose of ketamine, the level of cortisol will be decreased to a lesser extent than in case we use etomidate alone. measurement will be done peoperative and 6 hours after the procedure

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 20, 2021)

• Incidence of perioperative cardiopulmonary complications [ Time Frame: From preoperative till postoperative 6 hours ]
  1. Hypotension: decrease of baseline systolic blood pressure (SBP) >30%, or decrease of baseline diastolic blood pressure (DBP) >30%, and this was treated by phenylephrine 100-200 µg IV boluses.
  2. Bradycardia: decrease of HR < 50/min, and this was treated by atropine 0.5 mg IV boluses.
  3. Apnea: spontaneous breathing > 30 sec, or SpO2 < 85%, and this was treated by assisted manual ventilation using AMBU bag and face mask.
• Level of pateint satisfaction [ Time Frame: From preoperative till full recovery after 6 hours ]
  After full recovery and when the patients were alert enough to express their attitude regarding the intra-procedural events, they will be asked to score their level of satisfaction during the procedure in terms of recalling any painful or other undesirable intra-procedural events. Patient's satisfaction level will be assessed with a Likert five-item scoring system : (1 = Not satisfied at all, 2 = slightly satisfied, 3 = somewhat satisfied, 4 = very satisfied, and 5 = extremely satisfied).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Anesthesia for Upper Endoscopy and Colonoscopy in Cardiac Patients With Acute Anemia
• Official Title: Anesthesia for Upper Endoscopy and Colonoscopy in Cardiac Patients With Acute Anemia: Pretreatment With Low-dose Ketamine Can Reduce the Dose of Etomidate. A Randomized Clinical Trial.
• Brief Summary: The aim of this study was to try to reduce the required dose of etomidate used in anesthesia for upper endoscopy and colonoscopy in critically ill cardiac patients who complain of severe anemia in cardiac intensive care units by using a low dose of ketamine, which helps to reduce the side effects of etomidate, the most important of which is its suppressive effect on the adrenal gland and the secretion of cortisol in such critical cases, while maintaining hemodynamic stability, and the patient's satisfaction.

Detailed Description

This Prospective Randomized Clinical Trial will be done in the period from November 2020 - October 2021, after approval of our local ethical committee, and based upon written informed consent, included sixty cardiac patients, ASA physical statuses III or IV, admitted in CCU and SICU, and scheduled for upper endoscopy together with colonoscopy for diagnosis and management of acute anemia.

The study will be performed in the CCU or SICU with the presence of all emergency equipment's. The gastroenterologist who performed the colonoscopies will be blinded from the type of drugs used for sedation.

All patients will receive a colonic preparation protocol before the operation, and bowel cleansing will be performed, and all patients will be fasting 8 hours before the procedures.

Anesthesia management:

After establishment of IV access, standard monitoring will be performed (noninvasive blood pressure, ECG, SpO2, and BIS using (Masimo) monitor).

Nasal cannula for oxygen (6 l/min) will be connected to all patients, then midazolam 0.03mg/kg IV as a premedication, and fentanyl 1µg/kg IV will be injected to all patients.

By the means of sealed envelope technique, patients will be randomly divided into two groups:

Group (E): Received Etomidate 0.2 mg/kg IV over 30 seconds, followed by 0.05 mg/kg IV and repeated when needed.

Group (KE): Received Ketamine 0.5 mg/kg IV over 30 seconds then Etomidate 0.1 mg/kg IV over 30 seconds, followed by 0.05 mg/kg IV and repeated when needed.

The additional dose of etomidate will be determined by the anesthesiologist to achieve 4-5 sedation level of Ramsay Sedation Scale or BIS above 60.

Complications during procedure will be considered and defined as:

1. Hypotension: decrease of baseline systolic blood pressure (SBP) >30%, or decrease of baseline diastolic blood pressure (DBP) >30%, and this will be treated by phenylephrine 100-200 µg IV boluses.
2. Bradycardia: decrease of HR < 50/min, and this will be treated by atropine 0.5 mg IV boluses.
3. Apnea: spontaneous breathing > 30 sec, or SpO2 < 85%, and this will be treated by assisted manual ventilation using AMBU bag and face mask.

During the procedure the level of sedation will be assessed every five minutes after administration of anesthetic drugs using Ramsay Sedation Scale (RSS) [18]: (1 = Anxious or restless or both, 2 = Cooperative, 3 = Responding to commands, 4 = Brisk response to stimulus, 5 = Sluggish response to stimulus, 6 = No response to stimulus), in addition to BIS.

The use of standard monitoring will be continued until the patients were fully awake. At the end of the procedure, total etomidate dose, the duration of the procedure, and the recovery time of the patients were recorded.

After full recovery and when the patients are alert enough to express their attitude regarding the intra-procedural events, they will be asked to score their level of satisfaction during the procedure in terms of recalling any painful or other undesirable intra-procedural events.

Patient's satisfaction level willbe assessed with a Likert five-item scoring system [19]:

(1 = Not satisfied at all, 2 = slightly satisfied, 3 = somewhat satisfied, 4 = very satisfied, and 5 = extremely satisfied).

Serum cortisol before and 6 hours after the procedure will be estimated in this clinical trial to calculate the percentage of suppression in both groups.

Statistical Analysis:

Sample size was calculated using: Calculator.net Home / math / sample size calculator. Sample size of 30 cases in each group was calculated to have at least an 80% power to detect the expected differences between the two groups with respect to the primary goal.

Group comparison willbe performed between groups E and KE to analyze differences. Mean, standard deviation (SD), median, frequency, and percentage (%) will be used in the descriptive statistics of the quantitative and qualitative data. Mann-Whitney U test will be used in the analysis of quantitative independent data. Chi-square test will be used to analyze qualitative independent data, and Fischer's test will be used when chi-square test conditions were not met. For comparison of the sedation score data, hemodynamic parameters and SpO2 values, the repeated measurement analysis will be used. P value <0.05 will be considered statistically significant. SPSS v23.0 program will be used for all the analysis.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Sixty adult cardiac patients, older than 18 with ASA II or III physical status who underwent upper endoscopy together with colonoscopy for management of acute anemia in the cardiac intensive care units from November 2020 - October 2021. They were randomly divided into two groups. All patients received 0.05 mg/kg midazolam and 1µg/kg fentanyl slow IV as basal sedation and analgesia, then :

Group (E): Received Etomidate 0.1 mg/kg IV over 20-30 seconds, followed by 0.05 mg/kg IV and repeated when needed, and Group (KE): Received Ketamine 0.5 mg/kg IV over 20-30 seconds followed by Etomidate 0.05 mg/kg IV over 20-30 seconds and repeated when needed.

Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description:

All participants including care provider and outcome assessors will unaware of group allocation.

Primary Purpose: Supportive Care

Condition

• Anemia
• Cardiomyopathies
• Pulmonary Hypertension

Intervention

• Drug: Etomidate
  Received Etomidate 0.2 mg/kg IV over 30 seconds, followed by Etomidate 0.05 mg/kg IV and repeated when needed.
• Drug: Ketamine Hydrochloride
  Received Ketamine 0.5 mg/kg IV over 30 seconds then Etomidate 0.1 mg/kg IV over 30 seconds, followed by 0.05 mg/kg IV and repeated when needed.

Study Arms

• Sham Comparator: Etomidate
  Received Etomidate 0.2 mg/kg IV over 30 seconds, followed by 0.05 mg/kg IV and repeated when needed.
  Intervention: Drug: Etomidate
• Active Comparator: Ketamine-Etomidate
  Received Ketamine 0.5 mg/kg IV over 30 seconds then Etomidate 0.1 mg/kg IV over 30 seconds, followed by 0.05 mg/kg IV and repeated when needed.
  Intervention: Drug: Ketamine Hydrochloride

Publications *

• Corwin HL, Krantz SB. Anemia of the critically ill: "acute" anemia of chronic disease. Crit Care Med. 2000 Aug;28(8):3098-9.
• van Leerdam ME, Vreeburg EM, Rauws EA, Geraedts AA, Tijssen JG, Reitsma JB, Tytgat GN. Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000. Am J Gastroenterol. 2003 Jul;98(7):1494-9.
• Colle I, Wilmer A, Le Moine O, Debruyne R, Delwaide J, Dhondt E, Macken E, Penaloza A, Piessevaux H, Stéphenne X, Van Biervliet S, Laterre PF. Upper gastrointestinal tract bleeding management: Belgian guidelines for adults and children. Acta Gastroenterol Belg. 2011 Mar;74(1):45-66. Erratum in: Acta Gastroenterol Belg. 2011 Jun;74(2):368.
• Regula J, Sokol-Kobielska E. Sedation in endoscopy: when and how. Best Pract Res Clin Gastroenterol. 2008;22(5):945-57. doi: 10.1016/j.bpg.2008.06.002. Review.
• Habibi MR, Baradari AG, Soleimani A, Emami Zeydi A, Nia HS, Habibi A, Onagh N. Hemodynamic responses to etomidate versus ketamine-thiopental sodium combination for anesthetic induction in coronary artery bypass graft surgery patients with low ejection fraction: a double-blind, randomized, clinical trial. J Clin Diagn Res. 2014 Oct;8(10):GC01-5. doi: 10.7860/JCDR/2014/10237.5006. Epub 2014 Oct 20.
• Bovill JG. Intravenous anesthesia for the patient with left ventricular dysfunction. Semin Cardiothorac Vasc Anesth. 2006 Mar;10(1):43-8. Review.
• Forman SA. Clinical and molecular pharmacology of etomidate. Anesthesiology. 2011 Mar;114(3):695-707. doi: 10.1097/ALN.0b013e3181ff72b5. Review.
• Wanscher M, Tønnesen E, Hüttel M, Larsen K. Etomidate infusion and adrenocortical function. A study in elective surgery. Acta Anaesthesiol Scand. 1985 Jul;29(5):483-5.
• Heidari SM, Loghmani P. Assessment of the effects of ketamine-fentanyl combination versus propofol-remifentanil combination for sedation during endoscopic retrograde cholangiopancreatography. J Res Med Sci. 2014 Sep;19(9):860-6.
• Rai K, Hegde AM, Goel K. Sedation in uncooperative children undergoing dental procedures: a comparative evaluation of midazolam, propofol and ketamine. J Clin Pediatr Dent. 2007 Fall;32(1):1-4.
• Zed PJ, Mabasa VH, Slavik RS, Abu-Laban RB. Etomidate for rapid sequence intubation in the emergency department: is adrenal suppression a concern? CJEM. 2006 Sep;8(5):347-50. Review.
• Varga I, Rácz K, Kiss R, Fütö L, Tóth M, Sergev O, Gláz E. Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells. Steroids. 1993 Feb;58(2):64-8.
• Wu GN, Xu HJ, Liu FF, Wu X, Zhou H. Low-Dose Ketamine Pretreatment Reduces the Incidence and Severity of Myoclonus Induced by Etomidate: A Randomized, Double-Blinded, Controlled Clinical Trial. Medicine (Baltimore). 2016 Feb;95(6):e2701. doi: 10.1097/MD.0000000000002701.
• Elhamamsy MM, Aldemerdash AM, Zahran FB, Ezz GFM, AlSaud SA, Boules ML, Abdelhady MA, Hamed MA. Effects of adding low-dose ketamine to etomidate on serum cortisol levels in critically ill cardiac patients: a randomized clinical trial. BMC Anesthesiol. 2022 Apr 21;22(1):114. doi: 10.1186/s12871-022-01654-0.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 20, 2021): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 20, 2021
• Estimated Primary Completion Date: November 20, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• - Age 18 - 65 years,
• ASA II-III
• Ejection fraction (EF) > 30%.

Exclusion Criteria:- Poor left ventricular function (ejection fraction < 30%).

• Recent myocardial infarction (last seven days),
• Patients with uncontrolled chronic disease (uncontrolled diabetes mellitus (DM) and hypertension),
• Known history of hypersensitivity to midazolam, fentanyl, etomidate, Or ketamine,
• Severe respiratory, hepatic or renal failure,
• History of neurological disorders or convulsions,
• In addition, any need for further anesthetic drug administration other than the study protocol was another exclusion criterion of this study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mostafa M Elhamamsy, MD; 00966568799134; mostafah333@gmail.com

Contact: Rubie M. de Ocampo; 00966114691531; rdeocampo@ksu.edu.sa

• Listed Location Countries: Saudi Arabia

Administrative Information

• NCT Number: NCT04857450
• Other Study ID Numbers: E-20-4814
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All collected IPD
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: January 2022
• Access Criteria: IPD data will be available on request through email.

• Responsible Party: Mostafa Mohammed Elsaid Elhamamsy, King Saud University
• Study Sponsor: King Saud University
• Collaborators: Not Provided

Investigators

• Study Director: Rubie M de Ocampo; INSTITUTIONAL REVIEW BOARD King Saud University

• PRS Account: King Saud University
• Verification Date: April 2021