1. Postoperative respiratory depression associated with the perioperative use of intrathecal morphine at Auckland Hospital Nicola Broadbent Auckland City Hospital NZ

2. Aims To examine the usage of intrathecal morphine at Auckland Hospital Identify associated post-operative respiratory depression and/or sedation

3. Design Northern X Regional Ethics Committee and ADHB Research Office approval Retrospective 12 month period – Sept 2008 - Sept 2009 Patient group – Patients aged 16 years and over – Single dose of intrathecal morphine – Surgical procedures excluding obstetric and cardiac bypass procedures Controlled drug register Notes review to confirm administration Database compilation

4. Event data 24 hr period post intrathecal morphine dose Observations – Respiratory rate <8/min – SpO 2 <90% – GCS<9 – Worst AVPU score Interventions – Medical review sedation +/- respiratory rate – Naloxone administration – Code Red/Blue – HDU/ICU admission

5. Patient characteristics Total patients429 Sex [n(%)] Male221 (51.5) Female208 (48.5) Age in years [range(median)]16-96 (70) ASA score [n(%] 136(8.4) 2218(50.8) 3137(31.9) 419 (4.4) 50 (0) Not recorded19(4.4) BMI (kg/m 2 ) [range(median)] *information available for 302 patients only17.8-57.2 (27.6) Obstructive sleep apnoea [n(%)]7 (1.6) Obstructive pulmonary disease [n(%)]32 (7.5) Other documented respiratory diagnosis [n(%)]60 (14)

6. Surgical speciality 429 patients underwent 438 procedures 9 patients had 2 procedures

7. Anaesthesia Patients [n(%)] General anaesthesia261 (59.7) Regional anaesthesia+/- sedation176 (40.3) Elective procedure361 (82.4) Acute procedure77 (17.6)

8. Intrathecal morphine dose Dose range 50-500mcg Mean dose 158.5mcg Median dose 150 mcg 37 (8.4%) received a dose > 200mcg Intrathecal morphine dose (mcg)

9. Complications EventsProcedures [n (%)] Total events53 (12.1) Bradypnoea (RR <8/min)47 (10.7) Sedation with bradypnoea16 (3.7) Sedation without bradypnoea5 (1.1) SpO 2 <90% * 2 (0.5) Medical review for bradypnoea and/or sedation15 (3.4) Required intravenous naloxone6 (1.37) * 1 patient had preoperative hypoxia

10. Patients receiving naloxone Intrathecal morphine dose (mcg) Morphine prior to ward (mg) RR < 8/minSedationArterial blood gas Time to naloxone (hr) 54yr ♀ ASA not recorded Partial hepatectomy 27516Yes pH 7.33 PaO 2 17.5 PaCO 2 6.4 HCO 3 23 3.3 61yr ♀ ASA 3 Hepatico-jejunostomy 2504Yes pH 7.22 PaO 2 12.1 PaCO 2 7.9 HCO 3 20 11.5 67yr ♂ ASA 2 Excision of hydatid liver cyst 27510Yes pH 7.3 PaO 2 11.1 PaCO 2 7.0 HCO 3 23 14.5 D 70yr ♂ ASA 2 Hepatico-jejunostomy 20010Yes pH 7.23 PaO 2 23.3 PaCO 2 9.0 HCO 3 24 9.5 76yr ♂ ASA 2 Partial hepatectomy 3005NoYes pH 7.25 PaO 2 15.3 PaCO 2 8.1 HCO 3 23 5 80yr ♀ ASA 3 Nephro-uretectomy 1503Yes pH 7.25 PaO 2 21.1 PaCO 2 7.4 HCO 3 21 10.5

11. Opioid consumption Route of administrationProcedures [n (%)]Dose range (mg) Intravenous bolus morphine Intraoperative46 (10.5)1-20 PACU62 (11.9)1-30 Ward9 (2.1)1-7 PCA total248 (56.6) PCA morphine197 (45) PCA tramadol30 (6.8) PCA fentanyl20 (4.6) PCA pethidine1 (0.2) Oral opiates total69 (15.8) Sevredol56 (12.8)5-80 M-eslon6 (1.4)10-40 Oxynorm6 (1.4)10-30 Methadone4 (0.9)2.5-65 LA morph1 (0.2)200 Morphine infusion4 (0.5) Pethidine PCEA1 (0.2)

12. Sedative co-analgesics AnalgesicProcedures (n)Naloxone adminstered [n (%)] Gabapentin premedication364 (11.1) Intraoperative ketamine250 (0) Postoperative ketamine90 (0) Clonidine40 (0) Dexmedetomidine infusion10 (0)

13. Events by speciality SpecialityProcedures (n)RR <8/min [n (%)] Medical review required [n (%)] Naloxone given [n (%)] Orthopaedic surgery264 (60.3)14 (5.3)2 (0.8)0 (0) Urology83 (18.9)10(12)3 (3.6)1 (1.2) General surgery59 (13.5)19(32.2)10 (16.9)5 (8.5) Vascular surgery14 (3.2)0 (0) Thoracic surgery13 (3)4 (30.7)1 (7.7)0 (0) Gynaecology4 (0.9)0 (0) Aborted procedure1 (0.2)0 (0) High incidence of events requiring intervention in general surgical group – Hepatobilary patients responsible for all medical reviews and naloxone in this group

14. Hepatobiliary subgroup Predominant group contributing to respiratory and sedation events – 36/37 received dose of 200mcg or greater – Range 175-300mcg – Mean 252 mcg – Median 250mcg Patients[n(%)] Total37 Gabapentin premedication32 (86.4) Morphine prior PACU discharge19 (51.4) RR < 8/min13 (35.5) Medical review10 (27) Naloxone5 (13.5) Unplanned HDU admission4 (10.8)

15. How does this audit fit in the literature? AuthorYear published TypeCountryNo of patients Respiratory depression NNH Tramer et al2009Meta-analysisMultiple6451.2%84 Lim et al2006AuditAustralia4070.2% Gwirtz et al1999AuditUSA59693% Rawal et al1987SurveySweden~11030.38%275 Gustafsson et al1982SurveySweden~90-1504-7%

16. In summary In this retrospective QA project – 12.1% had a respiratory or sedative complication – 3.4% triggered a medical review – 1.37% needed iv naloxone for respiratory depression +/- sedation Features – Respiratory depression delayed 3.3-14.5 hr post dose – General surgical/hepatobiliary patients over-represented Larger intrathecal morphine doses Early iv morphine prior to PACU discharge Gabapentin premedication Conclusions – Orthopaedic patients can be nursed in ward setting with appropriate observations – Consider HDU placement for general surgical/hepatobiliary patients – Caution with early opiates and consider short acting opiates (eg fentanyl) for bridging – Caution with gabapentin premedication

18. Optimum dosing Optimization of the Dose of Intrathecal Morphine in Total Hip Surgery: A Dose-Finding Study Robert Slappendel et al. Anesth Anal 1999 88:822-6 – 143 pt receiving either 25,50,100,200mcg followed for 24hr – Optimal dose as low as 0.1mg. – 0.2mg did not improve analgesia but increased side effects Optimizing the dose of Intrathecal Morphine in Older Patients Undergoing Hip Arthroplasty Laffey et al Anesth Anal 2003. 97: 1709-15 – 60 pt receiving either 0, 50, 100, 200mcg followed for 24hr – 100mcg morphine provides best balance between analgesic efficacy Minimal effective dose of Intrathecal morphine for Pain Relief Following Transabdominal Hysterectomy Watanabe et al Anesth Anal 1989 – 188 pt receiving 30,40,60,80,100mcg followed for 48hr – Effective analgesia at 40mcg.

19. Hepatobiliary patients in the literature 2 recent studies The use of intrathecal morphine for postoperative pain relief after liver resection: A comparison with epidural analgesia – De Pietri et al Anesth Anal 2006 A change in practice from epidural to intrathecal morphine analgesia for hepato-pancreato-biliary surgery – Sakowska et al World J Surg 2009

22. Defining respiratory depression What do we mean? – Inadequate ventilation? – Bradypnoea? – Failure to oxygenate and clear waste gases? What can we measure on the ward? Definitions of "respiratory depression" with intrathecal morphine postoperative analgesia: a review of the literature – Goldstein et al. Can J Anesth 2003 – 96 studies – 46% did not define “respiratory depression” when used – 25% defined by respiratory rate alone SpO 2, ABG, naloxone treatment, carbon dioxide stimulation, level of sedation

23. Data collected Patient demographics Intrathecal morphine dose Surgical and anaesthetic details Other opioids – Early morphine consumption prior to PACU discharge – Presence/absence of PCA – Opioid usage over 24hr Sedative co-analgesics – Gabapentin premedication – Ketamine – Clonidine – Dexmedetomidine Pain scores

24. Bradypnoea (APS guidelines) Local guidelines recommend treatment with naloxone if RR <8/min and unrousable 5.2% had a RR of <8/min documented – 1.7% on surgical ward – 1 given naloxone