Journal Club October 17, 2013 Russell Quapp , PGY-4

1. Journal Club October 17, 2013 Russell Quapp, PGY-4

2. The post-operative sore throat • Incidence reports vary widely: • 6.6 – 90% • 21-65% • 53 – 57% with double lumen tubes • 25 – 57% • 100% ....

3. The post-operative sore throat (POST) • Etiology: • We stick something into peoples’ tracheas that don’t belong there.... • Risk factors • Preventative measures • Non-pharmacologic • Pharmacologic

4. Anesthesia and Analgesia; 2009. 40 patients in two groups.

5. Why might licorice work?

6. Why might licorice work? • Many active ingredients: • Glycyrrhizin – anti-inflammatory/anti-allergic properties • Glycyrrhizic acid – inhibits COX activity, PG formation, platelet aggregation • Liquilitin, Liquiritigenin glabridin – antitussives (peripherally/centrally) • Hispaglabridins – antioxidant/ulcer healing properties

8. Figure 1

10. Patient Demographics Surgery size: Small (thoracoscopy) Medium (thoracotomy <3h) Large (thoractomy >3h or blood loss >1000mL)

11. Protocol • Premedicated with oral midazolam (up to 7.5 mg) • Randomized: • Licorice extract • Sugar solution • Gargle for at least one minute sitting • Induction five minutes post gargling (fentanyl, propofol, rocuronium) • Intubation following loss of TOF with DL ETT (*unlubricated) with cuff pressures of 20 mmHg • Intra-operative analgesia with narcotics/paracetamol and a intercostal plexus block at the end of surgery • Extubated “while still anesthetized” • Post-operative analgesia with piritramide (synthetic opioid slightly weaker than morphine)

12. Measurement • Measurements were taken at 30 minutes, 90 minutes after arrival in PACU and 4 hours post extubation • 11 point Likert scale (0 – 10) • Also assessed pain on swallowing at 30 minutes. • Any score >0 defined as a sore throat. • Coughing assessed by observation and questioning the patient at 0, 30, 90 minutes post extubation. • None = 1 • Mild = 2 • Moderate = 3 (similar to common cold) • Severe = 4 • Above measures repeated on first morning post-op.

13. Interim Analysis Efficacy Futility Harm

14. Outcomes • Primary outcome: • Effect of licorice gargle on occurrence of sore throat at rest after intubation with DL ETT compared with sugar-water through the first four postextubation hours. • Secondary outcomes: • Effect of licorice on sore throat on postoperative day 1 • Incidence of sore throat during swallowing assessed at 0.5 hours post PACU arrival • Incidence of coughing over 5 time measurements • Amount of coughing over 5 time measurements

15. Analysis Measurements Statistical black box of number crunching Results

16. Results • Overall RR = 0.46 (0.29-0.72)

17. Results

18. Validity - Sniff test? • Seems to be okay – particularly for the primary outcome. • Do I care particularly about coughing end points? • Decreased coughing would likely be decreased pain in the post-thoractomy patient.

19. Validity – Clearly defined outcomes? • Primary • assess effect of licorice gargle on sore throat at rest after intubation with DL ETT compared with sugar water at 0.5, 1.5, 4 hours. • Secondary • Sore throat at rest POD 1 • Incidence of sore throat during swallowing at 0.5 hours • Overall difference in pain scores between at rest and swallowing at 0.5 hours and across four time points. • Incidence of coughing and amount/severity of coughing

20. Validity – Measurements • Pain vs. No pain • Objective outcome • Amount of pain (0-10) • More subjective, but validated scale • Incidence of coughing • Objective • Amount of coughing • Very subjective. • ? Validated (was published previously)

21. Validity - Randomization? • “Web-based” system used just prior to procedure. • Don’t state what system in particular was used…

22. Validity - Randomization – groups similar? • >0.2 standardized difference would indicate imbalance

23. Validity - Blinding? • Randomization with computerized system by “independent researcher” not involved in subsequent data collection • Licorice/sugar preparations by “independent apothecary” • Independent researcher not involved in data collection used to supervise gargling • Patients not told which solution they were using • Though likely could taste • Were only told they would be trying two different “sweet” solutions

24. Validity - Blinding? • Assessments in PACU were done by nurses “not present” for gargling • Possible patient’s could mention what flavor they had when gargling…. • Post-operative assessment on day 1 done by “independent and blinded investigator” • Again, possible that patient could mention/tell investigator what they had tasted

25. Validity - Intention to treat/loss to follow up? • One patient in each arm was lost to follow-up • Both remained intubated post surgery • Licorice group • Results were entered as “worst case scenario” • i.e. sore throat at all time points, coughing at all time points • Sugar group • Results entered as “best case scenario” • i.e. no sore throat at any time point and no coughing at any time point • Also one patient withdrawn secondary to emergency surgery

26. Validity - Similar to our patient population? • Looks similar

27. Limitations/Weaknesses • DL ETT vs. Single lumen ETT • Incidence with DL ETT likely higher • Would relative risk/treatment effect be as pronounced with single lumen tubes? • Previous study was with single lumen tubes • Thoracic/Thoracotomy patients • No documentation of comparability of opioids administered during cases. • Hopefully similar between groups • No documentation regarding airway grading/difficulty • Use of dexamethasone?

28. Limitations/Weaknesses • Why bother with the safety analysis? • Given the low pain scores in their study, how important a complication is it?

29. Will this change my practice? • Two studies now showing nearly identical results • 2 fold decrease in incidence of post-operative sore throat • Statistically significant results • Should this change my practice? • How much do I care about POST • Incidence seems relatively high • But how bad is it (very low pain scores in this study) • Is there any monetary cost (work days lost, prolonged hospital stay etc.) associated with POST • Doesn’t appear to be any harm, likely very inexpensive, potential benefit... • What about LMA’s?