CRITICAL APPRAISAL OF DIAGNOSTIC ARTICLE

1. JOURNAL CLUB CRITICAL APPRAISAL OF DIAGNOSTIC ARTICLE ALI A. ALBALUSHI EMERGENCY MEDICINE R- 4

2. Does End Tidal CO2 Monitoring During Emergency DepartmentProcedural Sedation and Analgesia With Propofol Decrease theIncidence of Hypoxic Events? Randomized, Controlled Trial Annals of Emergency Medicine Article in Press, 2009

3. Learning Objectives • Introduction • Discussion of the article • Critical appraisal of the article • Important calculations • Overview on LR

4. Introduction • Procedural sedation & analgesia for management of acute procedural pain & anxiety in the (ED) is part of core competency in emergency medicine. • A.C.E.P & A.S.A recommend continuous monitoring of PR & rhythm, RR, BP, & pulse oximetry during moderate and deep sedation

5. Introduction • Use of real-time capnography as adjunct to current procedural sedation safety and monitoring practice is under increasing scrutiny. • Capnography noninvasively measures the partial pressure of CO2 in exhaled breath & is tightly correlated with arterial CO2 in patients with normal lung function

6. Introduction • Minute ventilation is depressed by sedatives by reducing respiratory rate or tidal volume. • Respiratory depression may produce hypercapnia (RR > VT ) or hypocapnia (VT > RR )

7. Introduction • There is now compelling evidence that capnography identifies respiratory depression well before the onset of hypoxia. • This modality should allow physicians to intervene to improve ventilatory status.

8. Importance • Although pulse oximetry, PR, and BP monitoring are considered routine practice during ED procedural sedation & analgesia, capnography is not. • If the addition of capnography helps physicians reduces hypoxia, then perhaps it should also be routine.

9. Goal of Study • determine whether physician use of real-time capnography is associated with a 15% decrease in the incidence of hypoxia compared with standard monitoring alone during ED procedural sedation with propofol

10. Materials & Methods

11. Study Design • prospective, randomized controlled trial conducted from November 2006 to February 2008.

12. Setting & Selection of Participants • Study was conducted at Albert Einstein Medical Center, a 600-bed teaching hospital located in Philadelphia, with an annual ED census of 75,000 patients. • Enrolled consecutive (24 hours a day, 7 days a week) adults >18 years & selected for propofolsedation in accordance with their usual practice

13. Setting & Selection of Participants • Exclusion critiria: * severe chronic obstructive pulmonary disease; * chronic oxygen requirements; * hemodynamic instability; * respiratory distress; * pregnancy; *Inability to provide informed consent; * allergy to propofol, morphine, or fentanyl (or other components of its formulation); * or if, in judgment of the attending emergency physician, procedural sedation could compromise patient safety. Informed consent was obtained from each subject.

14. Setting & Selection of Participants • Pts randomly assigned to study group (standard monitoring and capnography) or control group (standard monitoring and blinded capnography) by research associates using computer-generated randomization list. • Research associates & treating physicians were blinded to the randomization choice until after enrollment.

15. Setting & Selection of Participants • Inaddition to standard electronic monitoring, they attached a Capnostream 20 monitor, using a nasal-oral CO2 cannula capable of delivering compressed gasses, with an oral sampling port to accommodate mouth breathers

16. Setting & Selection of Participants • Capnostream 20 monitor displays oximetry and CO2 waveform and calculates ETCO2. • All patients had capnography; • for the blinded (control) group, the monitor screen was adjusted to permit visualization only by the research associate.

17. Setting & Selection of Participants • All patients received supplemental oxygen at 3 L/minute by nasal cannula. • If the treating physician wished to deliver additional oxygen during the sedation, a nonrebreather mask connected to wall oxygen at 15 L/minute was placed over the cannula. • All patients received 0.5 g/kg of fentanyl or 0.05 mg/kg of morphine for analgesia no fewer than 30 minutes before administration of propofol for sedation.

18. Setting & Selection of Participants • They started with propofol 1 mg/kg, administering additional boluses of 0.5 mg/kg until desired level of sedation was achieved. • Patients closely monitored from the initiation of sedation until they were back to their baseline alertness and ready for discharge.

19. Data Collection and Processing • Data were collected by trained research associates, physicians who had participated in previous sedation studies & had no duties other than patient enrollment and data recording. • They were trained in procedural sedation & analgesia, study protocol and its definitions, all monitoring devices, and signs of respiratory depression.

20. Data Collection and Processing • They recorded age, sex, medical history, Rx, allergies, types of procedures performed, vital signs, & sedation and procedure times on a standardized data collection instrument. • The patient’s level of alertness was assessed at baseline, 90 s after preprocedure drug administration, & before discharge, using a modified Ramsay scale

21. Data Collection and Processing • Before the study, physicians & nurses trained in identification of respiratory depression with capnography • Treating physicians were instructed to perform procedural sedation and analgesia according to standard protocol • Any intervention for an adverse event should be based on their judgment and clinical expertise with or without capnography, depending on randomization arm.

22. Data Collection and Processing • Capnostream 20 records data electronically every 5 seconds during course of each sedation, • Research associates used electronic marking and time stamping to record specific events such as drug administration, beginning and end of procedure, and point of readiness for discharge

23. Data Collection and Processing • They noted time and nature of any intervention for respiratory depression or hypoxia, such as verbal or physical stimulation, airway realignment, use of additional oxygen, and the use of airway adjuncts, assisted ventilation, or intubation. • Research associates manually recorded other sedation-associated adverse events, including hypotension, bradycardia, arrhythmia, vomiting, prolonged ED stay, or admission

24. Outcome Measures • Electronic data from each sedation were downloaded from the monitor into a Microsoft Excel 2000 database & were checked for any discrepancies, with handwritten notations taken by the research associates. • printed time evaluation graph of the patient’s sedation was then produced

25. Outcome Measures

26. Outcome Measures • Before study blinding was broken, 3 investigators evaluated each graph to code the presence or absence of hypoxia & respiratory depression. • Hypoxia was defined a priori as an SpO2 level of less than 93% for 15 seconds or greater. • Respiratory depression was defined a priori as an ETCO2 level of 50 mm Hg or greater, an absolute increase or decrease from baseline of 10% or greater, or a loss of waveform for 15 seconds or greater

27. Outcome Measures • Grafs disqualified if they had greater than 35% data loss, unless all 3 evaluators agreed that there was unequivocal evidence of hypoxia or respiratory depression. • Lost data were typically due to patient movement (ie, dislodgement of the cannula) or blood pressure cuff insufflation.

28. Primary Data Analysis • Data analyzed descriptively & using χ2, with P<.05 considered significant. All analyses were with SPSS version 10. • Previous research has reported rates of hypoxia during ED propofol sedation ranging from 15% to 30%. • To identify a 15% decrease in hypoxia from a 20% presumed baseline, they calculated that they would need 72 pts in each arm (assuming a 1-tailed analysis, a power of 80%, and an α of 5%).

29. RESULTS

30. Characteristics of Study Subjects

31. Characteristics of Study Subjects

32. Main Results

33. Main Results majority of patients who developed respiratory depression had an ETCO2 change greater than 10% from baseline loss of waveform was most likely to lead to hypoxia.

34. Main Results • With capnography there were more physician interventions to improve respiratory status, 24 of 68 (35%) versus 14 of 64 (22%; difference 13%; 95% CI –2% to 27%)

35. Limitations • They had a higher-than-expected disqualification rate, leaving slightly less than calculated 72 patients per group for analysis. • However, they found a significant difference in their main outcome, and thus the study was not underpowered

36. Limitations • The observed rate of hypoxia (32.5%) was higher than that observed in most other studies of propofol for ED procedural sedation. • A rate of hypoxia more consistent with previous studies may have produced a smaller, nonsignificant difference between groups

37. Limitations • possibly that the continuous electronic data collection using the Capnostream 20 influenced the rate of hypoxia because it would detect episodes that might otherwise be missed through recording only at spaced intervals or through human inattention or error.

38. Limitations • unlikely that any device error contributed to the higher-than-expected rates of hypoxia and respiratory depression • It is possible that, if the clinicians had used greater amounts of supplemental oxygen, there would have been less overall hypoxia

39. Limitations • They chose a priori an SpO2 of 93% as baseline level for hypoxia because they believe that most physicians will pay close attention and potentially intervene at this level. • A lower threshold would have resulted in less overall hypoxia.

40. Discussion • Rate of hypoxic events decreased by using capnography in conjunction with standard monitoring. (17%) • Capnographic respiratory depression occurred before the onset of hypoxia and was temporally linked to subsequent hypoxic events.

41. Discussion • every patient who developed hypoxia had a corresponding ETCO2 change. • the increased sensitivity of the near-continuous electronic data capture with the Capnostream 20 allowed to measure this effect.

42. Discussion • Capnography can provide early warning of ventilatory abnormalities, alerting physicians to respiratory depression before the onset of a hypoxic event. • Using capnography in this study, emergency physicians improved pt safety by decreasing rate of hypoxic events ass. with procedural sedation & analgesia

43. Discussion • a number of patients had respiratory depression & hypoxia & treating physician did not intervene, with the episodes resolving spontaneously. • If every incidence of respiratory depression had led to an intervention, it is possible that there would have been less hypoxia

44. CRITICAL APPRAISAL

45. 1. Are the results in the study valid ?

46. Primary Guide • Was there an independent, blind comparison with a reference standard ? • Did the pt sample include an appropriate spectrum of pts to whom the diagnostic test will be applied in the clinical practice ?

47. Secondary guide • Did the results of the test being evaluated influence the decision to perform the reference standard ? • Were the methods for performing the test described in sufficient detail to permit replication ?

48. What are the results? Are LR for the test results presented or data neccessery for their calculation provided ?

50. Results • Sensitivity = a /a+c (TP among diseased) = 17 / 17 = 1 = 100% • Specificity = d /b+d (TN among non diseased) = 29 / 51 = 0.57 = 57%