Propofol VS Midazolam - Randomized Controlled Trial In Prosedural Sedation


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Research carried out In the Emergency Department USM and presented at International Conference in EM in San Francisco April 2008

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Propofol VS Midazolam - Randomized Controlled Trial In Prosedural Sedation

  1. 1. <ul><ul><ul><li>A Randomized Controlled Trial On Procedural Sedation Among Adult Patients At Emergency Department Hospital Universiti Sains Malaysia: Comparing Fentanyl With Midazolam Versus Fentanyl With Propofol </li></ul></ul></ul>12TH. INTERNATIONAL CONFERENCE ON EMERGENCY MEDICINE SAN FRANCISCO, USA 3RD - 6TH APRIL 2008 Nik HNA Rahman 1 (MBChB, MMed), R Ahmad 2 (MD, MMed) A Hashim 3 (MBBS, MMed) (Emergency Physicians) 1 Head of Department of Emergency Medicine, Hospital Universiti Sains Malaysia 2 Lecturer in Emergency Medicine, Hospital Universiti Sains Malaysia 3 Head of Accident & Emergency Department, Queen Elizabeth Hospital, Sabah Hospital Universiti Sains Malaysia, Kubang Kerian, 16150, Malaysia. Tel: 00609-766 3000, Fax: 00609-765 3370 Email:
  2. 2. INTRODUCTION <ul><li>Patients attended the emergency department for any forms of trauma and critically ill conditions frequently presented with physical or mental pain and agitation. </li></ul><ul><li>Some of them will require extra acute painful procedure in the ED as a form of treatment i.e fracture reduction, wound management, cardioversion. </li></ul><ul><li>In HUSM, we conducted in average approximately 35 cases per month in 2007. (65% orthopedic procedures, 30 % surgical/wound management, 5% medical cases) </li></ul>
  3. 3. INTRODUCTION <ul><li>Such patients would be subjected to some forms of chemical induction to facilitate the procedure planned to either save their lives or salvage the remaining functioning organs or limbs. </li></ul><ul><li>The procedure known as “Procedural Sedation” would involve a collective decision to choose the most appropriate form of chemical induction for the purpose of analgesia or sedation </li></ul><ul><li>This procedure is not without risk i.e effects of drugs, insufficient sedation etc </li></ul><ul><li>Typically in HUSM we use a combination of analgesics & sedatives (fentanyl, morphine, midazolam, ketamine etc) </li></ul>
  4. 4. INTRODUCTION <ul><li>The choice of drugs depends on the general medical conditions of patients, potential adverse events, efficacy/potency, duration of action etc. </li></ul><ul><li>The main goals of procedural sedation and analgesia are to give patients some relief from both pain and anxiety during the procedure while the patient maintains his/her own airway with minimal or NO adverse events </li></ul><ul><li>In addition to that this technique must be effective in reducing the stress response and improves patient’s compliance to undergo a procedure. </li></ul>
  5. 5. INTRODUCTION <ul><li>Potential & well known adverse events: deep sedation, hypotension, respiratory depression/desaturation, allergies, prolong sedation. </li></ul><ul><li>Statistically in HUSM in 2007: adverse events in all procedural sedation 55% respiratory depression, 25% hypotension, 8% airway obstruction, 3% Arrhythmias, 9% others </li></ul><ul><li>Commonly associated drugs with adverse events: midazolam, morphine, ketamine </li></ul><ul><li>Therefore the procedure must be done in a controlled environment by experience staff </li></ul>
  6. 6. INTRODUCTION <ul><li>In this study we explored the use of IV propofol & fentanyl compare with midazolam & fentanyl. </li></ul><ul><li>Propofol is a short/rapid acting hypnotic agent which when given via intravenous route the effect is almost immediate. </li></ul><ul><li>Sedative, analgesic, bronchodilating, antiemetic, reduce cerberal oxygen consumption </li></ul><ul><li>However it causes: apnoea, hypercapnia, hypotension, pain at injection site </li></ul><ul><li>Basset et al (2002) and Guenther et al (2000) have showed that with a bolus dose of 1mg/kg followed by 0.5 mg/kg (titration) may reduce both the hypoxia and apnea </li></ul>
  7. 7. STUDY OBJECTIVES <ul><ul><li>Aim of the Study </li></ul></ul><ul><ul><ul><li>To initiate the creation of a standard or comparable protocol for procedural sedation delivered at the Emergency Department setting in Hospital Universiti Sains Malaysia. </li></ul></ul></ul><ul><ul><ul><li>To evaluate the importance of using capnography routinely when procedural sedation is given at the Emergency Department setting. </li></ul></ul></ul>
  8. 8. STUDY OBJECTIVES <ul><li>General Objective </li></ul><ul><li>To compare the safety and efficacy between combination of fentanyl and propofol with combination of fentanyl and midazolam in procedural sedation. </li></ul><ul><li>(Side effects) </li></ul><ul><li>Specific Objectives </li></ul><ul><li>To compare the outcomes between combination of fentanyl and propofol with fentanyl and midazolam on subjects during and after a procedural sedation. </li></ul><ul><li>(MAP, Oxygen saturation, ETCO2, time to recovery) </li></ul>
  9. 9. METHODOLOGY <ul><ul><ul><li>Null Hypothesis </li></ul></ul></ul><ul><ul><ul><ul><li>The use of combined fentanyl and propofol has no difference over fentanyl and midazolam for procedural sedation </li></ul></ul></ul></ul><ul><ul><ul><li>Population </li></ul></ul></ul><ul><ul><ul><ul><li>Adult patients who full fill the criteria for the procedural sedation </li></ul></ul></ul></ul><ul><ul><ul><li>Intervention </li></ul></ul></ul><ul><ul><ul><ul><li>Administration of either fentanyl with midazolam or fentanyl with propofol </li></ul></ul></ul></ul>
  10. 10. METHODOLOGY <ul><li>Randomized control trial study which was carried out at the Emergency Department, University Hospital over a period of 12 months commencing from December 2006 until May 2007. </li></ul><ul><li>The proposal of this study was presented to the Department Board Review and Hospital Ethical Committee. Short term grant was awarded for the research by the University. ( USMKK/PPSP®/JK P&E 2006) </li></ul><ul><li>70 patients were recruited and randomized using computer generated random permuted blocks of four patients and were divided equally into two groups (n=35 each group) </li></ul><ul><li>Single patient blinded to the drugs used </li></ul>
  11. 11. METHODOLOGY <ul><li>Drugs were supplied by the HUSM pharmacy and were wrapped individually and placed in sealed envelope labeled accordingly as drug A or drug B </li></ul><ul><li>The research operators were the on-call emergency physician and the senior trainee in EM </li></ul><ul><li>All identified patients for procedural sedation were placed in procedural room well equipped with resus. Equipments </li></ul><ul><li>Both verbal and written consent were obtained as required by the University Research Ethical Committee </li></ul>
  12. 12. METHODOLOGY <ul><li>Standard monitoring of systolic and diastolic BP, HR, RR, O2 saturation & ETCO 2 were carried out to each patient selected into the study </li></ul><ul><li>Patients were randomly allocated to one of the two groups: </li></ul><ul><ul><li>Group A - Subjects received IV Fentanyl 1 mcg/kg as a bolus dose and Propofol 1mg/kg followed by Propofol 0.5mg/kg if needed. </li></ul></ul><ul><ul><li>Group B - Subjects received IV Fentanyl 1 mcg/kg as a bolus dose and a bolus dose of Midazolam 0.1mg/kg and 0.1mg/kg if needed. </li></ul></ul>
  13. 13. METHODOLOGY <ul><li>Titrating dose of sedatives were used until the patients achieved either Ramsay Sedation Score of 3 or 4 </li></ul>
  14. 14. METHODOLOGY <ul><li>Vital signs were monitored/recorded for every 5 minutes including the adverse events </li></ul><ul><li>The time of regaining full consciousness in each subject was charted upon the completion of the procedure. </li></ul><ul><li>Upon regaining full consciousness subjects would be reviewed by attending medical officer before decision is made for the disposal </li></ul><ul><li>The data was analyzed using SPSS program version 12.0 </li></ul><ul><li>(vital signs, time to discharge, adverse events) </li></ul>
  15. 15. RESULTS The youngest subject that has been recruited in this trial was 13 years of age while the oldest being 78 years old with the mean age of 37.8 years In subjects receiving propofol, the mean age was 39.52 ± 17.64 while for midazolam the mean age of subjects was 37.00 ± 15.58 (p>0.05)
  16. 16. RESULTS MAP dropped for both drugs BUT p>0.05 MAP improved post procedures Prior to discharge Respiratory rate increased slightly Intraprocedure and normalized post procedure (Both drugs) (P=0.106)
  17. 17. RESULTS No significant dropped in O 2 Saturation for both drugs No significant change in ETCO 2
  18. 18. RESULTS Decreased Decreased Decreased Unchanged Unchanged Unchanged Unchanged BUT P>0.05
  19. 19. RESULTS
  20. 20. DISCUSSION <ul><li>This study aimed to evaluate the safety profile and effectiveness between the two sedative-hynotics namely the propofol and midazolam which have been commonly used in patients undergoing procedural sedation </li></ul><ul><li>This trial which took 6 months to complete involved seventy (n=70) subjects who had fully consented to participate. There was no drop-out </li></ul><ul><li>This study was dominated by male subjects that make almost 80% of the sample. This follows the general trend: victims of trauma/soft tissue injury which predominates in male group </li></ul>
  21. 21. DISCUSSION <ul><li>As a whole this study did not show remarkable differences between the two drugs used namely propofol and midazolam (MAP, Respiratory rate, O2 sat.) </li></ul><ul><li>Both drugs did not cause any serious adverse side effects throughout the study such as hypoventilation, hypotension, apnea, hypoxia or allergy reaction </li></ul><ul><li>These findings were consistent and supported the study done by Gabopoulou et al. (2005) on procedural sedation using intravenous propofol for 48 patients undergoing elective orthopaedic surgery under regional blockade </li></ul><ul><li>Cheol H.P et al (2006) who conducted a randomized double blind comparative study using propofol alone and combined propofol and midazolam in colonoscopy have found that both propofol alone and combined propofol and midazolam are safe and effective </li></ul>
  22. 22. DISCUSSION <ul><li>This study has shown beyond any doubt that propofol is much more superior than midazolam in term of duration taken for patients to regain full consciousness after procedural sedation has been delivered </li></ul><ul><li>The shorter time taken to reverse a patient undergoing procedural sedation after a procedure had been completed may offer excellent indication to use propofol in the emergency setting (twice longer in midazolam group) </li></ul><ul><li>Based on RCT involving 96 patients, Riphau et al found that the mean recovery time was significantly better in patients who received propofol sedation than midazolam with the time taken to recover was reported to be 14 minutes versus 25 minutes with p value < 0.01 </li></ul>
  23. 23. DISCUSSION <ul><li>This study utilized ETCO 2 monitoring for early detection </li></ul><ul><li>of respiratory/cardiovascular compromise state </li></ul><ul><li>In this study, the ETCO 2 in propofol group did not show much variation between the pre and intra procedural readings </li></ul><ul><li>Similar finding for the midazolam group was noted </li></ul><ul><li>This is due to the fact the dose of both drugs used were safe to cause sedation without complications </li></ul><ul><li>Crespo AS. 1997, pointed out that capnography is capable of providing important data regarding cardiorespiratory & metabolic status & could replace the need to analyze ABG in the non invasive manner </li></ul>
  24. 24. DISCUSSION <ul><li>Dang K. (1998) has stressed the significance of unrecognized respiratory difficulty and hypoxeamia as a major factor to contribute morbidity and mortality among patients with procedural sedation in the ambulatory setting </li></ul><ul><li>Dang strongly recommended the use of capnography which has the ability to monitor and detect any evidence of respiratory compromise early with combined use of pulse oxymetry </li></ul><ul><li>(Dang K. 1998). </li></ul>
  25. 25. CONCLUSION <ul><li>This study has proven the null hypothesis, where there were no difference in the complications between the study drugs midazolam and proporfol during procedural sedation </li></ul><ul><li>Both propofol and midazolam given at the recommended doses are equally safe and effective in procedural sedation that is performed at the emergency department setting </li></ul><ul><li>Propofol has been found to shorten the recovery process after procedural sedation at the emergency department setting and is a drug of choice over midazolam </li></ul>
  26. 26. CONCLUSION <ul><li>Propofol could be recommended to be used in the emergency department for any procedural sedation if the emergency physicians are trained and familiar with the use of the drug </li></ul><ul><li>Capnography is a very important mean of monitoring and detecting End tidal carbon dioxide during procedural sedation </li></ul><ul><li>The procedural sedation should be carried out in a controlled environment i.e with the presence of monitoring and resuscitation equipment. </li></ul>
  27. 27. REFERENCES <ul><ul><ul><li>Andrea Riphaus, T. G., Markus B. Frenz, Till Wehrmann (2006). &quot;Quality of Psychomotor Recovery After Propofol Sedation for Routine Endoscopy: A Randomized, Controlled Study.&quot; GASTROINTESTINAL ENDOSCOPY Volume 63, No. 5 . </li></ul></ul></ul><ul><ul><ul><li>Charles M, M. H., Wehner P, Marshall University School of Medicine, and W. W. F. U. S. o. M. Huntington, Winston-Salem, NC (2005). &quot; Propofol for Procedural Sedation in the Pediatric Patient.&quot; Annals of Emergency Medicine S73 Volume 46, no. 3 : September 2005 . </li></ul></ul></ul><ul><ul><ul><li>Gabopoulou Z., M. P. P. L., Boura D., and K. M. Vrettou V., Velmachou K. &quot;conscious sedation with propofol during elective orthopeadic surgery under regional blockade.&quot; anesthesia . </li></ul></ul></ul><ul><ul><ul><li>M.Jung, C. H., R. Kiesslich, A, Brackertz (2000). &quot;Improved sedation in Diagnostic & therapeutic ERCP: propofol is an alternative to Midazolam.&quot; Endosopy endoscopy 2000;32:233-238 . </li></ul></ul></ul><ul><ul><ul><li>Anninen PH, C. A., Papworth D (1997). &quot;conscious sedation for interventional neuroradiology: a comparison of midazolam & propofol infusion.&quot; anesthesia . </li></ul></ul></ul><ul><ul><ul><li>Yehoshua Colman, B. K. (1999). &quot;microstream capnography technology: a new approach to an old problem.&quot; Clinical monitoring and computing 15:403-409 . </li></ul></ul></ul>