Surgery – PICO #2

Brief description of patient problem/setting (summarize the case very briefly)

While watching an anesthesiologist induce a patient to become intubated for their laparoscopic appendectomy, the anesthesiologist mentions she is using propofol. You remember the last anesthesiologist used etomidate. You know that both anesthetics have different indications for them, and wonder if both can be used together to optimize both drugs synergistically during intubation.

Search Question: Clearly state the question (including outcomes or criteria to be tracked)

Does the combination of propofol and etomidate incite more hemodynamic stability for patients being induced for surgery versus propofol or etomidate alone?

Question Type: What kind of question is this? (boxes now checkable in Word)

☐Prevalence                             ☐Screening                  ☐Diagnosis

☐Prognosis                              ☐Treatment                 ☒Harms

Assuming that the highest level of evidence to answer your question will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)? Please explain your choices.

– If meta-analysis or systematic review are not available, randomized controlled clinical trials will also offer great supporting evidence as they are carefully planned experiments, reduce the potential for bias, and allow for comparison between intervention and control groups.

– Cohort studies could also be used since they allow to follow the patients who have already received a particular treatment forward over time. This is not as reliable as randomized controlled clinical trials since patients might differ in ways other than in the variable that is being observed.

PICO search terms:

Surgical intubationPropofol and EtomidatePropofolHemodynamic stability
IntubationCombination of Propofol and EtomidateEtomidateStable Blood Pressure
Induction of General AnesthesiaEtomidate and Propofol  
 Propofol plus Etomidate  

Search tools and strategy used:

Please indicate what data bases/tools you used, provide a list of the terms you searched together in each tool, and how many articles were returned using those terms and filters.
Explain how you narrow your choices to the few selected articles.

Results found:

TRIP Database

  • Induction of Anesthesia AND Combination of Propofol plus Etomidate – 39
  • Induction of Anesthesia AND Combination of Propofol and Etomidate – 9


  • Induction of Anesthesia AND Combination of Propofol and Etomidate (in the last 10 years) – 23

Google Scholar

  • Induction of Anesthesia AND Combination of Propofol and Etomidate (in the last 10 years) – 16,100
  • Induction of Anesthesia AND Combination of Propofol plus Etomidate (in the last 10 years) – 4,910

For many of the articles I had to sift through different anesthetic combinations (like propofol and ketamine or etomidate and fentanyl). Thankfully, there were many randomized control trials to look through, as well as meta-analysis and systematic reviews. One of the articles below is from a Turkish journal, but I felt it fit with my PICO question and supported the other articles I had before it. Many of the same conclusions were found with that study as with the others.

Identify at least 3 articles (or other appropriate reputable sources) that answer your specific question with the highest available level of evidence (you will probably need to look at more than 3 articles to get the 3 most focused and highest-level articles to address your question). Please make sure that they are Medline indexed.

Please post the citation and abstract for each article (to include the journal and authors’ names and date) and say why you chose it.
Please also note what kind of article it is (e.g. meta-analysis, cohort study, or independent blind comparison with gold standard of diagnosis, etc.).

At the bottom of each abstract, please comment on what your key points are from this article (including any points or concepts included in the article, but not present in the abstract – i.e. make the concepts understandable to the reader)

Please note that if the evidence is not in the abstract, you must clearly summarize the evidence in your posting.

Citation: Li, Y., Lu, W., Li, D., Zhou, J., Applegate, R., Liu, H. (2021). Comparison of the combination of propofol and etomidate versus propofol or etomidate alone for induction of general anesthesia: a double-blind, randomized controlled trial. Archives of Medical Science.
Type of article: Double-blind, randomized controlled trial
Abstract   Introduction Hemodynamic fluctuation during the induction of general anesthesia is a common event and adversely affect patients’ outcomes. The aim of this study is to investigate the impacts of different anesthesia induction agents: propofol, etomidate, and propofol-etomidate combination on patient hemodynamics and processed electroencephalography (EEG).   Material and methods Seventy-five patients undergoing elective non-cardiac surgery were randomly assigned to three groups of anesthesia induction agents: the group P received 2 mg/kg propofol, the group E received 0.3 mg/kg etomidate, and the group PE received the combination of 1mg/kg propofol plus 0.15mg/kg etomidate. Hemodynamic variables and processed EEG were measured during induction.   Results Heart rate (HR) was significantly increased at intubation and 1 min after intubation compared with baseline in all three groups. Mean arterial pressure (MAP) decreased significantly after induction, at 5, and 10 min after intubation in group P (79.1±12.6, 77.0±14.2, 76.6±11.4 versus 93.2±9.9 mmHg; all P<0.001). MAP increased significantly at intubation and 1 min after intubation in group E (104.7±13.0, 103.8±12.8 versus 92.9±10.2; P<0.001, P=0.001 respectively). The incidence of myoclonus was lower in groups PE (4.0%) and P (4.0%) compared with that in group E (24.0%) (P=0.033). The incidence of pain at injection was higher in group P (28.0%) than that in groups PE and E (4.0% and 0.0%) (P=0.025).   Conclusions The combination of propofol and etomidate used during induction of anesthesia provided a more stable BP profile, less pain at site of injection, and decreased myoclonic movements compared with propofol or etomidate alone.
Key Points: This double-blind randomized control study was comprised of 75 patients who were randomly assigned to three different groups of anesthesia induction agents who were undergoing elective non-cardiac surgeryA third of the patients were given propofol at 2 mg/kgThe second third of patients were given 0.3 mg/kg of etomidateThe final third of patients were given a combination of 1 mg/kg propofol plus 0.15 mg/kg etomidateMean arterial pressure (MAP) was decreased for the group who were given propofol, while MAP was increased for the group that was given etomidateCompared to the groups who were given etomidate or propofol, the group that were given the combination of drugs saw a more stable blood pressure profile throughout the surgery, as well as less pain at the injection site and decreased jerky movements
Why I chose it: I chose this article because it was one of the few articles that included both the combination of propofol and etomidate and saw how their effects were in comparison to each drug separately. I wish the number of patients were greater in total, but the equal number of patients in each of the groups was great to have. Ultimately, the combination of etomidate and propofol had a greater hemodynamic profile to the patients who were part of that group, than with the other groups who had etomidate or propofol alone
Citation: Chen, Lingyuan BSa; Liang, Xueyan MMa; Tan, Xinmei MMb; Wen, Haibin MMc; Jiang, Junsong MMd,∗; Li, Yan MMa,∗. Safety and efficacy of combined use of propofol and etomidate for sedation during gastroscopy: Systematic review and meta-analysis. Medicine 98(20):p e15712, May 2019. | DOI: 10.1097/MD.0000000000015712
Type of article: Systematic review and meta-analysis
Abstract: Background: Sedation with etomidate or propofol alone during gastroscopy has many side effects. A systematic review and meta-analysis were conducted to evaluate the safety and efficacy of the combined use of propofol and etomidate for sedation during gastroscopy. Methods: PubMed, Embase, Medline (via Ovid SP), Cochrane library databases, CINAHL (via EBSCO), China Biology Medicine disc (CBMdisc), Wanfang, VIP, and China National Knowledge Infrastructure (CNKI) databases were systematically searched. We included randomized controlled trials (RCTs) comparing the combined use of propofol and etomidate vs etomidate or propofol alone for sedation during gastroscopy. Data were pooled using the random-effects models or fixed-effect model based on heterogeneity. Results: Fifteen studies with 2973 participants were included in the analysis. Compared to propofol alone, the combined use of propofol and etomidate possibly increased recovery time (SMD = 0.14, 95% CI = 0.04–0.24; P = .005), and the risk for myoclonus (OR = 3.07, 95% CI = 1.73–5.44; P < .001), injection pain, and nausea and vomiting. Furthermore, compared to propofol alone, the combination of propofol and etomidate produced an apparent beneficial effect for mean arterial pressure (MAP) after anesthesia (SMD = 1.32, 95% CI = 0.38–2.26; P = .006), SPO2 after anesthesia (SMD = 0.99, 95% CI = 0.43–1.55; P < .001), apnea or hypoxemia (OR = 0.16, 95% CI = 0.08–0.33; P < .001), injection pain, and body movement. Further, compared to etomidate alone, the combination of propofol and etomidate reduced the risk for myoclonus (OR = 0.15, 95% CI = 0.11–0.22; P < .001), body movement, and nausea and vomiting. Conclusion: The combination of propofol and etomidate might increase recovery time vs that associated with propofol, but it had fewer side effects on circulation and respiration in patients undergoing gastroscopy. The combined use of propofol and etomidate can improve and produce an apparent beneficial effect on the adverse effects of propofol or etomidate alone, and it was safer and more effective than propofol or etomidate alone.
Key Points: This article included a meta-analysis and systematic review of 15 randomized control trialsThe 15 RCTs involved 2,973 patients with the number of patients in the studies ranging from 80 to 400 patientsRecovery time was increased for those patients who were induced with propofol and etomidate togetherMAP was more stable and more effective for the patients that were given the combination of drugs than those who were given propofol by itselfThe patients given the combination of etomidate and propofol has lower instances of hypotension in comparison to those who were given propofol by itselfThe combined use of propofol and etomidate caused minimal respiratory depression versus propofol aloneThe combined use of etomidate and propofol also caused less myoclonus on patients than etomidate did by itselfEtomidate by itself was shown to increase the risk of nausea and vomiting, while propofol and etomidate reduced the riskOverall, the combination of propofol and etomidate was shown to be safer in many respects compared to using propofol or etomidate alone
Why I chose it: I chose this article because there were many factors that made up the study. It was the first meta-analysis that included a very large patient study. There were 116 articles that the authors could have chosen from, but they ultimately narrowed it down to 15 RCT studies, which shows me that they screened the studies they chose very well. The combination of propofol and etomidate had lower instances of hypotension, more stable blood pressure throughout the surgery, less myoclonic effects on the body, lower instances of nausea and vomiting, and minimal respiratory depression versus having either of propofol or etomidate by itself
Citation: Vikram, S. R., Singh, S., Taank, P., Khandelwal, A., & Kaushal, A. (2019). Clinical Analysis of Propofol, Etomidate and an Admixture of Etomidate and Propofol for Induction of General Anesthesia. Turkish Journal of Anesthesiology & Reanimation, 47(5), 382-386.
Type of article: Double-blind, randomized controlled trial
Abstract Objective: To compare the clinical outcome following induction of general anesthesia with intravenous (IV) injection of propofol (P), etomidate (E) or a 50% admixture of propofol and etomidate (PE). Methods: In this prospective, randomized, double-blind controlled study, patients 18–60 years of age who were undergoing elective surgery with general anesthesia were randomized to receive either propofol 2.5 mg kg−1 IV (group P; n=30), etomidate 0.3 mg kg−1 IV (group E; n=30) or an admixture of etomidate 0.2 mg kg−1 IV and propofol 1 mg kg−1 IV (group PE; n=30) as the induction agent. The hemodynamic response was first recorded at baseline, then at 1 minute following administration the study drug, and 1, 3, 5, 10-, 20-, 30- and 40-minutes following intubation. Perioperative symptoms such as myoclonus, pain upon injection and/or vomiting upon induction as well as postoperative nausea were recorded. Results: We observed a decrease in systemic hemodynamics from baseline following induction in group P compared to groups E and PE (p<0.05). Incidence of myoclonus was reduced from 76.6% in group E to 6.6% in group PE (p<0.001). There was also a reduction in reported pain upon injection in group PE compared to group P (p<0.001). Although we found no statistically significant difference between the three groups when assessing postoperative nausea and vomiting, these symptoms were more prevalent in groups E and PE than in group P. Conclusion: Using an admixture of etomidate and propofol as the induction agent reduced the incidence of side effects observed with use of either drug alone such as pain upon injection, myoclonus, and hemodynamic instability.
Key Points: This double-blind randomized control trial study looked at 90 patients who were split up into three groupsGroup P got 2.5 mg/kg of IV propofolGroup E got 0.3 mg/kg of IV etomidateGroup PE got a mixture of etomidate 0.2 mg/kg and 1 mg/kg of propofolHeart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and oxygen saturation were measured in increments following intubationFor assessments of pain a 4-point grading scale was used (0 – no pain to 3 – very painful) For myoclonus a 4-point grading scale was used (0 – no myoclonus to 3 – hypertonia of neck or trunk)Postoperative nausea was recorded as grade 0, 1, 2 and 3 as no, mild, moderate, and severe nausea.Heart rate and oxygen saturation remained stable across all three groupsMean arterial pressure dropped in Group P, as well as diastolic blood pressure, as compared with the other two groupsIncidence of myoclonic movements were at 76.6% with Group E, while Group PE had an incidence of only 6.6% of any jerking movementsPost-operative nausea and vomiting were higher in Group E, than they were in group PE and Group P
Why I chose it: I chose this article because it reconfirmed what a lot of the other articles showed us. It was a double-blind randomized control trial with more participants in it than the first article we talked about. The groups were evenly disseminated throughout the trial. We saw that etomidate alone increased myoclonic activity in its patients, and propofol alone induced hypotension in its patients. The mixture of both drugs had much less adverse effects for either complication

What is the clinical “bottom line” derived from these articles in answer to your question?

Propofol and etomidate are two commonly used I.V. induction agents with fast onset and short duration of action. However, they have different clinical impacts and side effect profiles. Propofol tends to cause hypotension during induction and causes induration at the injection site, while etomidate produces myoclonic movements in patients as well as nausea and vomiting. Interestingly, propofol inhibits myoclonus, nausea, and vomiting caused by etomidate. Combining propofol and etomidate would not only decrease the required dose of either medication and provide the known benefits of both agents, it also prevents the hemodynamic changes that occur due to propofol or etomidate administration alone.

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