Postoperative respiratory depressionassociated with the perioperative use of

intrathecal morphine at Auckland Hospital

Nicola BroadbentAuckland City Hospital

NZ

Aims

To examine the usage of intrathecal morphine at Auckland Hospital

Identify associated post-operative respiratory depression and/or sedation

DesignNorthern 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

Event data• 24 hr period post intrathecal morphine dose

• Observations– Respiratory rate <8/min– SpO2<90%– GCS<9– Worst AVPU score

• Interventions– Medical review

• sedation +/- respiratory rate

– Naloxone administration– Code Red/Blue– HDU/ICU admission

Patient characteristicsTotal patients 429

Sex [n(%)]

Male 221 (51.5)

Female 208 (48.5)

Age in years [range(median)] 16-96 (70)

ASA score [n(%]

1 36(8.4)

2 218(50.8)

3 137(31.9)

4 19 (4.4)

5 0 (0)

Not recorded 19(4.4)

BMI (kg/m2) [range(median)] *information available for 302 patients only 17.8-57.2 (27.6)

Obstructive sleep apnoea [n(%)] 7 (1.6)

Obstructive pulmonary disease [n(%)] 32 (7.5)

Other documented respiratory diagnosis [n(%)] 60 (14)

Surgical speciality

26483

59

14 13

4 1

Orthopaedic (60.3%)Urology(18.9%)General surgery (13.5%)Vascular surgery (3.2%)Thoracic surgery (3%)Gynaecology(0.9%)No procedure (0.2%)

429 patients underwent 438 procedures9 patients had 2 procedures

Anaesthesia

Patients [n(%)]General anaesthesia 261 (59.7)Regional anaesthesia+/- sedation 176 (40.3)

Elective procedure 361 (82.4)Acute procedure 77 (17.6)

Intrathecal morphine dose

<100

100 125 150 175 200 225 250 275 300 325 350 375 400 425 450 475 5000

20

40

60

80

100

120

140

160

Dose range 50-500mcgMean dose 158.5mcgMedian dose 150 mcg

37 (8.4%) received a dose > 200mcg

Intrathecal morphine dose (mcg)

Complications

Events Procedures [n (%)]

Total events 53 (12.1)

Bradypnoea (RR <8/min) 47 (10.7)

Sedation with bradypnoea 16 (3.7)

Sedation without bradypnoea 5 (1.1)

SpO2 <90%* 2 (0.5)

Medical review for bradypnoea and/or sedation 15 (3.4)

Required intravenous naloxone 6 (1.37)

* 1 patient had preoperative hypoxia

Patients receiving naloxoneIntrathecal morphine dose (mcg)

Morphine prior to ward (mg)

RR < 8/min Sedation Arterial blood gas Time to naloxone (hr)

54yr ♀ASA not recordedPartial hepatectomy

275 16 Yes Yes pH 7.33 PaO2 17.5 PaCO2 6.4 HCO3 23

3.3

61yr ♀ASA 3Hepatico-jejunostomy

250 4 Yes Yes pH 7.22 PaO2 12.1PaCO2 7.9 HCO3 20

11.5

67yr ♂ASA 2Excision of hydatid liver cyst

275 10 Yes Yes pH 7.3 PaO2 11.1 PaCO2 7.0 HCO3 23

14.5

D 70yr ♂ASA 2Hepatico-jejunostomy

200 10 Yes Yes pH 7.23 PaO2 23.3PaCO2 9.0 HCO3 24

9.5

76yr ♂ASA 2Partial hepatectomy

300 5 No Yes pH 7.25 PaO2 15.3PaCO2 8.1 HCO3 23

5

80yr ♀ASA 3Nephro-uretectomy

150 3 Yes Yes pH 7.25 PaO2 21.1 PaCO2 7.4 HCO3 21

10.5

Opioid consumptionRoute of administration Procedures [n (%)] Dose range (mg)

Intravenous bolus morphine

Intraoperative 46 (10.5) 1-20

PACU 62 (11.9) 1-30

Ward 9 (2.1) 1-7

PCA total 248 (56.6)

PCA morphine 197 (45)

PCA tramadol 30 (6.8)

PCA fentanyl 20 (4.6)

PCA pethidine 1 (0.2)

Oral opiates total 69 (15.8)

Sevredol 56 (12.8) 5-80

M-eslon 6 (1.4) 10-40

Oxynorm 6 (1.4) 10-30

Methadone 4 (0.9) 2.5-65

LA morph 1 (0.2) 200

Morphine infusion 4 (0.5)

Pethidine PCEA 1 (0.2)

Sedative co-analgesics

Analgesic Procedures (n) Naloxone adminstered [n (%)]

Gabapentin premedication 36 4 (11.1)

Intraoperative ketamine 25 0 (0)

Postoperative ketamine 9 0 (0)

Clonidine 4 0 (0)

Dexmedetomidine infusion 1 0 (0)

Events by specialitySpeciality Procedures (n) RR <8/min [n (%)] Medical review

required [n (%)]Naloxone given [n (%)]

Orthopaedic surgery 264 (60.3) 14 (5.3) 2 (0.8) 0 (0)

Urology 83 (18.9) 10(12) 3 (3.6) 1 (1.2)

General surgery 59 (13.5) 19(32.2) 10 (16.9) 5 (8.5)

Vascular surgery 14 (3.2) 0 (0) 0 (0) 0 (0)

Thoracic surgery 13 (3) 4 (30.7) 1 (7.7) 0 (0)

Gynaecology 4 (0.9) 0 (0) 0 (0) 0 (0)

Aborted procedure 1 (0.2) 0 (0) 0 (0) 0 (0)

High incidence of events requiring intervention in general surgical group– Hepatobilary patients responsible for all medical reviews and naloxone in this

group

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(%)]

Total 37

Gabapentin premedication 32 (86.4)

Morphine prior PACU discharge 19 (51.4)

RR < 8/min 13 (35.5)

Medical review 10 (27)

Naloxone 5 (13.5)

Unplanned HDU admission 4 (10.8)

How does this audit fit in the literature?

Author Year published

Type Country No of patients

Respiratory depression

NNH

Tramer et al 2009 Meta-analysis Multiple 645 1.2% 84

Lim et al 2006 Audit Australia 407 0.2%

Gwirtz et al 1999 Audit USA 5969 3%

Rawal et al 1987 Survey Sweden ~1103 0.38% 275

Gustafsson et al 1982 Survey Sweden ~90-150 4-7%

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

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.

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

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

• SpO2, ABG, naloxone treatment, carbon dioxide stimulation, level of sedation

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

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