There are no safe drugs, only

safe ways of using them

Voltaire 1694-1778

Prof Nerida Smith

School of Pharmacy, Gold Coast campus
Griffith University, Queensland 4222 Australia
Hospital errors killed golfball teen: coroner
Thu Jan 24, 2008
A coroner has found Sydney's Royal North Shore (RNS) Hospital made almost every
conceivable error in its treatment of a teenage girl, whose "tragic" death was "avoidable".

Sixteen-year-old Vanessa Anderson died at the RNS in November 2005, two days after
she was hit on the head by a golf ball.

Deputy state coroner Carl Milovanovich re-opened the inquest in July last year after
fresh allegations emerged about a doctor central to the case.

The inquest heard anaesthetist Sanaa Ismial gave Ms Anderson the wrong dose
of a painkiller.
Mr Milovanovich has found the teenager died of respiratory arrest due to the effect of the
medication she was administered.

He referred to mistakes in judgement and a failure in communication, and recommended

a full and open inquiry into the state's health system.
Children at risk of medication error halves
Sydney Morning Herald November 20, 2008

The number of children who die, become ill or are put at risk of harmful
side-effects from medication prescribed during their stay in hospital has
dropped by more than half over the past four years, a project at the Sydney
Children's Hospital has found.

But despite the improvements, almost nine out of every 100 pediatric
patients prescribed drugs during their stay in hospital experiences or
narrowly avoids an adverse drug event.

The most common causes of medication error are staff's failure to read or
misreading charts, slips in attention, particularly after hours and when busy,
and distracted staff dealing with unfamiliar patients.

In response, children's hospitals throughout Australia have developed a

standardised chart for all inpatients.
A poor state of health: NSW
hospitals the worst in the country
January 29, 2010
• Adverse Drug Events (ADEs)
– Adverse drug reactions
– Medication errors

• Medication-related injury in high risk

situations Interfaces with the health system
ED/Inpatient
– Elderly Hospital/community
– Children Aged Care
– Complex regimens Specialist/GP
– Low safety margin medications
 ......ADRs hospital admission

• 5-fold increase in ADR associated admissions 1981-

2002

• Increases in medication use correlates with ADRs

associated with hospitalisation

• 1.3% of admissions associated with an ADR that

required treatment
– A further 0.3% had an untreated ADR
– A further 1.2% had an ADR during their stay

Carrol et al. Aust Health Rev 2003; 26:100-105.

Runciman et al. Int J Qual Health Care 2003; 15(Supp 1):i49-i59.
 • 3% of attendances at the Emergency
Department for children were due to ADEs
– Conventional medications
– Complementary and alternative medications

• 50% potentially preventable

Easton-Carter et al. J Paediatr Child Health 2003; 39(2):124-9.

Taylor et al. Emerg Med Australasia 2004; 16(5-6):400-406.
Roughead & Semple. Review for the Aust Commission on Safety & Quality in
Healthcare, 2008
 Hospitals can be risky places......
• ADRs are often under-reported

• 26% of 27,000 hospital-related incidents were medication-

related
– < 5% ADRs
– Majority involve dose omission, overdose, wrong medicine,
underdose

• Patients on warfarin
– 5% have an INR > 5
– 1% have abnormal bleeding
– 0.05% have cerebral haemorrhage
– 0.2% die

Runciman et al. Int J Qual Health Care 2003; 15(Supp 1):i49-i59.

 • ADRs in Oncology patients
– 74% of admissions associated with an ADR
(median 2/admission)

– 47% potentially preventable

– Impact on life
0 = no impact 6 = totally changed my life
• 53% rated 4 +
• 19% “totally changed my life”

Lau et al. Support Care Cancer 2004; 12:626-633.

• ADEs in the elderly
– up to 30% of hospital admissions and re-
admissions for 75+ year olds are medication
related

– ADRs 10 – 25%

– 30% potentially preventable

Chan et al. Intern Med J 2001; 31(4):199–205.
Runciman et al. Int J Qual Health Care 2003; 15(Supp 1):i49-i59.
Witherington et al. Qual Saf Health Care 2008; 17(1):71-5.
Roughead & Semple. Review for the Aust Commission on Safety & Quality in
Healthcare, 2008
 ADR Communication
• Directors of Pharmacy surveyed
– 49.5% responded
– 61% centralised ADR reporting (pharmacists)
– 18% assessed preventability of ADRs
– 22.5% gave feedback to reporters
– 62% gave general feedback
– 13% rewarded reporters

• Notified
– 96% patient (91% verbal, 17% card, 13% letter)
– 89% GP (15% via patient, 70% discharge
summary, 26 % letter)
– 11% community pharmacist
 And on return to the community.....

• 20% of those > 65 years receiving home

care after hospital discharge report an ADE

• General practice - up to 25% of “high risk”

patients reported experiencing an ADE in the
previous three months

Gray et al. Ann Pharmacother1999; 33(11):1147-53.

Sorenson et al. Age Ageing 2005; 34(6):626-32.
 Drugs implicated in ADRs

• Anticoagulants • Cardiac glycosides

• Anti-inflammatories • Diuretics
• Opioids • Antihypertensives
• Steroids • Hypnotics
• Antineoplastics • Anticonvulsants
• Antibiotics • Antipsychotics
• Hypoglycaemics
Roughead & Semple. Review for the Aust Commission on Safety & Quality in
Healthcare, 2008.
“I stopped taking the medicine
because I prefer the original
disease to the adverse drug
reactions.”
 Adverse Drug Reaction

• Any response to a drug which is

noxious, unintended and occurs at
doses used in humans for
prophylaxis, diagnosis or therapy
• WHO, 1976
 Adverse Drug Reactions
Lee, Adverse Drug Reactions, 2001

Type A Type B
Augmented Bizarre
Predictable Yes No
Dose- Yes No
dependent
Incidence High Low
Morbidity High Low
Mortality Low High
Management Adjust dose Stop drug
 A
• Inhaled corticosteroids for
asthma prevention

• Impaction of steroid 
– Immunosuppression
+
– Overgrowth of commensal candida
albicans

Reduce exposure: Rinse after inhalation. Use a spacer.

Reduce frequency of exposure: once or twice daily (not 3 – 4 times/day)
 A
– Additive anticoagulant effects 
bleeding

• Warfarin

• Ginkgo biloba
G • Glucosamine
• Ginseng
• Ginger
• Guarana
• Garlic
 B
• Pharmaceuticals in herbals
– NZ: herbal remedies for
eczema, asthma, arthritis
(Shen Loon, Cheng Kum)
• Contained potent corticosteroid
 “remarkable” cures
+/- Cushing’s Syndrome

• Substitution of one herb for another

(more toxic) herb
– Periploca sepiu instead of Siberian Ginseng
 “hairy baby case”
(androgenisation of mother + infant)
 B
The Courier-Mail March 27, 2007
Stilnox callers jam hotline

• CONCERNS are rising over the controversial

sleeping drug Stilnox (zolpidem),
with 300 callers swamping a consumer
information line detailing dangerous side-effects,
including sleep walking over high-rise balconies.

• Sydney man Brett Crealy, 33, is lucky to have survived plunging from a
12-storey hotel balcony on Queensland's Hamilton Island in late
February after taking Stilnox.

• A Brisbane woman in her 40s had her leg amputated at Princess

Alexandra Hospital in December after taking Stilnox for the first time.
"She was taken to hospital after being found in the bathroom
unconscious a day after falling on her leg," said pharmacist Geraldine
Moses, of Australia's Adverse Medicine Events Line. "She'd cut off the
circulation for so long it had gone gangrenous."
 Why do ADRs still occur and
remain unrecognised as ADRs?
• Prescribers and patients may be reluctant to accept that
treatment has resulted in harm

• ADR may mimic a common symptom

• ADR confused with symptom of disease

• ADR is not easily associated with drug

being prescribed - EVENT MONITORING

• Delay between drug administration and ADR onset

 Why aren’t ADRs detected
pre-marketing?
• Numbers!
To detect one case with 95% CI, must study 3 x ADR
incidence “Rule of 3”
– Idiosyncratic ADRs 1:10,000
– Need n=30,000 in Phase 3 sample to detect ADR
– Phase 3 sample usually n= 3,0000

• Post-marketing population is diverse

– Known risk factors, uncontrolled regimen, concomitant drugs
and diseases

• Surveillance usually voluntary

 Examples of drug withdrawals

• Troglitazone 90x hepatoxicity:

– Thiazolidinedione; Type 2 diabetes 68 deaths
– 1997: marketed
10 transplants
– 2000: withdrawn
– Known liver problems, benefits > risks (??)

• Bromfenac
– NSAID; orthopaedic pain 50x hepatoxicity
– 1997: marketed (uncontrolled use)
– 1998: withdrawn
– Expected liver ADRs; <10 day treatments
 Preventing ADRs
• Take a careful history

• Start Low, Go Slow

• Adjust dose to therapeutic end-points

• Adjust dose to optimum Cplasma

• Adjust dose to RF, LF, Diseases, Drugs

renally excreted drugs
•Only 26% of 38 patients weighed before prescribing
•45% of 192 patient admitted with poor renal function had too high
a dose
Hilmer et al 2007; Med J Aust 37:647-650; Pillans et al 2003; Intern Med J 33: 10-13.
• Who can report ADRs?
– Doctors, pharmacists, dentists,
nurses, herbalists, general public
…. anyone!
Medicine
• What ADRs can be reported? Herb
– Serious
Vaccine
– Unexpected
– New Device
Blood product
• Reports are sent to WHO - data added to world-
wide data base
Aust Commission on
Safety and Quality in
Healthcare
 Hospital errors
• 26 staff interviewed
Patient impact
• 29 medication errors in 25 patients 13 wrong dose
– 21 slips and lapses 10 wrong drug
11 drug with-held
(prescribing, dispensing, administration) 1 wrong patient
– 8 knowledge based
(prescribing)

• Contributors
– Individual, team, patient, environmental
– Inadequate knowledge
• 23% Accessing protocols and guidelines
• 23% Accessing drug dosing information
• 27% Unfamiliar drug
– 30% Communication problems Nichols et al. 2008; Med J Aust
188:276-279.
– 31% Unfamiliar with patient
• 21 prescribing errors by hospital interns
– 90 % Environmental factors
(workload, skill mix)
– 76% Team factors
(communication, supervision)
– 76% Individual factors
(knowledge and skills, motivation)
– 76% Task factors
(Med chart design, protocols, test results)
– 62% Patient factors
(patient condition, communication)

Coombes et al. 2008; Med J Aust 188:89-94.

 • 154 registered nurses in regional hospitals
– 51% responded
– 25% Interruptions and distractions
– 25% Stress, high workload
– 17% Fatigue, lack of sleep
– 13% Poor communication
– 29% “I need further training in medication
administration”
• Other studies:
– High workloads, high doctor expectations
– Good knowledge protects against errors
– Importance of systems in preventing errors identified
Deans C. 2005; Collegian 12:29-33
Roughead & Semple. Review for the Aust Commission on Safety & Quality in
Healthcare, 2008.
 Discharge Prescription errors

• Prescribing errors on discharge prescriptions:

• 5% Handwritten Rx

• 11.6% Computer-generated Rx
– Excessive duration (antibiotics→default quantity)
– Dosing errors
– Including ceased medications
Coombes et al 2004; Med J Aust 180:140-141.
 Pharmacy errors

• Hospital
– dispensing error rates 0.08% - 0.8%
– Potential for patient harm not reported

• Community pharmacy
– “mystery shoppers” 24%
– voluntary reporting and < 10%
direct observation

Allan et al. Am Pharm 1995; NS35(12): 25-33.

 General Practice
• Medications prescribed to 1000 high risk GP patients
– 115 errors per 100 patients

• 25% of medical negligence claims involving GPs

– Prescribing, monitoring, administering
• Anticoagulants
• Anti-inflammatories
• Opioids
• Antibiotics
• IM iron

Gilbert et al. Med J Aust 2002: 13(2):101-4.

Bird S, 2002; Aust Fam Phys 31(12)
Tuesday 20 April 2010
Improving patient medication safety in Australia

World Health Organization’s High 5s Project

28 hospitals across Australia will introduce standardised procedures to collect and

check information about each patient’s medicine

From admission through each stage of treatment when medicines may change

The GP receives an accurate and comprehensive list of the medicines

 https://www.high5s.org

WHO 2006 - Patient Safety collaboration

• Reduce 5 challenging patient safety problems in 5

countries over 5 years.
Australia, Canada, Germany, the
Netherlands, NZ, UK, USA,
France, Saudi Arabia, Singapore
1. Assuring medication accuracy
at transitions in care
2. Managing concentrated
injectable medicines
3. Performance of correct
procedure at correct body site
4. Communication failures during
patient handovers
5. Addressing health care-
associated infection
 Assuring medication accuracy
at transitions in care:
Medication reconciliation
• "The interface between different care settings is particularly prone to
error and a potential target for interventions to reduce medication
error.”
Easton, K., T. Morgan, et al. (2008). Medication safety in the community: A review
of the literature. Sydney, National Prescribing Service.

• Matching the medicines the patient should be prescribed to those they

are actually prescribed.
– Admission to hospital

– Transfer from the Emergency Department to other care areas

– Transfer from the Intensive Care Unit to the ward

– From hospital to home, ....

 Medication Reconciliation Project
• 28 hospitals
• 5 year project
• Testing SOP for assuring medication accuracy at transitions
in care using medication reconciliation process
• Phase 1: medication reconciliation for patients > 65 years
ED→ Inpatient Ward
• Phase 2: roll-out across all patients and all entry points to
inpatient and outpatient settings
• Canada, France, Netherlands, Singapore, UK, USA
• On-line information system: learning community,
benchmarking
• National Medication Reconciliation Seminar 11th Oct 2010
Sydney
 Managing concentrated
injectable medicines
• Patients have died after
being mistakenly injected
with Potassium Chloride
instead of Normal Saline

• Numerous “near misses”

• Recommendations
– Wards: Remove ampoules of KCl and replace with
pre-mix
– Critical care: Risk assess if KCl needed as stock.
Develop SOP for safe preparation and use.
– Store KCl and pre-mixes separately
 KCl amps / Pre-mix Progress

• 2003 Pre-mix introduced

KCl amps removed from Qld Health Formulary

• 2005 24,000 KCl amps/month used

(91 % by ICUs)

• Suitable Pre-mix minibag produced

– 75% users satisfied
– Unclear labelling, packaging differences (imported product)
– Australian product sourced (improved labelling and packaging)
– Endorsed by Qld ICU network
– Statewide roll-out
 Statewide Medication Chart
• Multidisciplinary collaboration of 7 hospitals
• Standardised medication chart with revised ADR
documentation and warfarin management
• Trialled and evaluated
2002 2007
– Patient identification 57% 83%
– Weight recorded 12% 7%
– ADR history recorded73% 89%
– ADR details recorded 28% 53%
– Missing PRN frequencies 23% 22%
– Unclear PRN frequencies 37% 35%
– INRs > 5 1.9% 1.2%
 It’s in your Vest Interest
• Medication Round Safety Vest
on trial in Australian hospitals

• "Research has shown that the introduction of

Medication Safety Vests will act as a visible
outward sign, reducing distractions for nursing
staff administering medications."
— Queensland Health

• www.reflective-fabrications.com.au/safety-clothing/healthcare.html
 New roles for pharmacists

• Liaison Pharmacist
– Target patients “at risk”
– Hospital discharge process
– Home visits
• Warfarin
• Chronic heart failure
• Emergency Department Pharmacist
– Medication reconciliation
– Drug information
– Tablet identification
– ED drug stock
– Staff education
– .....
 Many more exciting initiatives
to improve Medication Safety
• E-Health
• Automated dispensing and distribution
• Bar coding/scanning
• Labelling and packaging
• Academic detailing
• Education and training
• Systems-based approaches
• .......