There are no safe drugs only safe ways

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 Interfaces with the health system situations 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 19812002 • 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): i 49 -i 59.

• 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 medicationrelated – < 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): i 49 -i 59.

• 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 readmissions 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): i 49 -i 59. 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% – 89% – 11% patient GP (91% verbal, 17% card, 13% letter) (15% via patient, 70% discharge summary, 26 % letter) 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 Pharmacother 1999; 33(11): 1147 -53. Sorenson et al. Ageing 2005; 34(6): 626 -32.

Drugs implicated in ADRs • • Anticoagulants Anti-inflammatories Opioids Steroids Antineoplastics Antibiotics Hypoglycaemics • • • Cardiac glycosides Diuretics Antihypertensives Hypnotics Anticonvulsants Antipsychotics 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 Augmented Yes Type B Bizarre No Dosedependent Incidence Yes No High Low Morbidity High Low Mortality Low High Management Adjust dose Stop drug Predictable

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 G • Ginkgo biloba • 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 Stilnox callers jam hotline The Courier-Mail March 27, 2007 • 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 40 s 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 – – 90 x hepatoxicity: Thiazolidinedione; Type 2 diabetes 68 deaths 1997: marketed 10 transplants 2000: withdrawn Known liver problems, benefits > risks (? ? ) • Bromfenac – – 50 x hepatoxicity NSAID; orthopaedic pain (uncontrolled use) 1997: marketed 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? – Serious – Unexpected – New Herb Vaccine Device Blood product • Reports are sent to WHO - data added to worldwide data base

Aust Commission on Safety and Quality in Healthcare

Hospital errors • 26 staff interviewed • 29 medication errors in 25 patients – 21 slips and lapses (prescribing, dispensing, administration) – 8 knowledge based (prescribing) Patient impact 13 wrong dose 10 wrong drug 2 drug with-held 1 wrong patient • Contributors – Individual, team, patient, environmental – Inadequate knowledge • 23% • 27% – 30% – 31% Accessing protocols and guidelines Accessing drug dosing information Unfamiliar drug Communication problems Unfamiliar with patient Nichols et al. 2008; Med J Aust 188: 276 -279.

• 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; NS 35(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 5 s 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. high 5 s. 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 careassociated 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 11 th 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 recorded 73% 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. . . .