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Safe Prescribing Week 3 – Amino glycosides + electrolytes Dr Ian Coombes, Senior Clinical Lecturer University of Queensland Schools of Medicine and Pharmacy.

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Presentation on theme: "Safe Prescribing Week 3 – Amino glycosides + electrolytes Dr Ian Coombes, Senior Clinical Lecturer University of Queensland Schools of Medicine and Pharmacy."— Presentation transcript:

1 Safe Prescribing Week 3 – Amino glycosides + electrolytes Dr Ian Coombes, Senior Clinical Lecturer University of Queensland Schools of Medicine and Pharmacy Safe Medication Practice Unit, Queensland Health Dr Ian Coombes, Senior Clinical Lecturer University of Queensland Schools of Medicine and Pharmacy Safe Medication Practice Unit, Queensland Health The University of Queensland

2 Objectives Principles of once daily Aminoglycoside dosing and avoiding toxicity Key messages about analgesia use

3 Gentamicin Revision Gram negative bactericidal agent Excellent anti-pseudomonal cover Once daily dosing benefits vs tds or bd: - high peak level – excellent distribution - post antibiotic effect (>24-36 hours) - reduced monitoring and administration - reduced nephro and ototoxicity - easier monitoring (10-12 hours post dose)

4 Severe risks of nephrotoxicity and ototoxicity Mrs HR 78 years, wt 57kg Admitted to outlying hospital acute exacerbation COPD Baseline Cr 80  mol/L Charted gentamicin 160mg daily for 5/7 CrCl = 45ml/min

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7 21/6 Gent level still 1.4!!!! 23/6 complaining of dizziness, unsteady feeling, vestibular symptoms, vomiting 1/7 Cr 0.21 recovering

8 Aminoglycoside dosing and Monitoring Case continued… Day 3: Mr AD (67yrs) has now developed sever hospital acquired pneumonia Ward round decisions - start gentamicin once a day  dose as per levels each night at 20:00  recall patient weighs 70 kg  creatinine has improved (now 140 micro mole/l) - start Co-Amoxiclav 1.2g IV q8h

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10 Creatinine Clearance Do NOT use eGFR provided by AusLab (calculated using standard 70 kg patient  can lead to over-dosing) Recall Cockcroft-Gault Formula: CrCl (mL/min) = [140-age (years)] * ideal weight (kg) [0.814 * serum creatinine (micromol/L)] { ♀ * 0.85 } If patient 70 kg, 67 y.o. with serum creat~140micromol/L: CrCl ≈ 42 mL/min ( X 70) / (0.814 x 140)

11 Ideal Body Weight male = 50kg + (0.9 * [ height (cm) – 152]) female = 45.5kg + (0.9 * [ height (cm) – 152]) or ideal weight = BMI 25 BMI = weight (kg) / [height (m)] 2  ideal weight = 25 * [height (m)] 2 or height (cm) – 100 = weight (kg)

12 Calculating first dose gent

13 Gentamicin Dose Adjustment Day 4:  gentamicin level = 2.5 (taken 08:00, 12 hrs post dose) The initial dose given in emergency department was 280mg (4mg/kg x approx 70kg) Prescribe new gentamicin dose based on level

14 2.5

15 Adjusting doses of gentamicin

16 Gentamicin Dose Adjustment Level at 12 hours = 2.5 (ideal = < 2) New Dose = Level Wanted (mg/L) x Dose Given (mg) Level Achieved (mg/L) In this case: (1.5/2.5) x 280 = 168 mg round down to 160 (nearest multiple of 40 mg) - amps = 40 mg/mL

17 When NOT to take levels Do not take levels if: Stat dose Or Patient has Normal renal function and is only receiving 1 or 2 doses ie prophylactic

18 Variable Dose Medication Drug Level and Time Taken Dose Time and Actual Time Given

19 Use in moderate to sever renal function Where ever possible withhold other nephrotoxic drugs and ensure no other altenative Ie unavoidable use of gentamicin: Requires extended dose intervals 36, 48 or 96 hours Effectively daily levels wait til < 1.0mmol/l then dose again

20 Gentamicin FAQs Patient returns from OT, septic, at 4 p.m.? - dose now - get level 8 a.m. (difficult to get bloods during night)  if level < 0.5, clearance satisfactory Patient in ED at 4 a.m. with severe pneumonia? - give standard dose now; dose again at 8 p.m. Level low but adequate dose? (patient ok clinically) - dose 4-5mg/kg has long post antibiotic effect - don’t increase If in doubt, CHECK! - Registrar; clinicial pharmacists; ID team

21 Gentamicin Ordering key messages If elderly (renal impaired) is there an alternative safer drug? Do not write as a regular medication – prescribe dose for regular dosing after levels available Dose according to gentamicin level Use aminoglycoside dosing guides - these notes safe prescribingwww.wiki.tox.org.2.17 Try to prescribe in multiples of 40mg (ampoule contains 80mg/2mL = 40mg/mL) Where possible, dose at a time that allows level to be taken on next day’s blood round

22 Questions?

23 Introduction to Prescribing Analgesia and Pain Relief Presented by: [insert presenter name here]

24 You have been asked to write up a patient’s analgesia… What patient factors do you need to consider?

25 Patient Assessment Goal to individualise analgesic therapy Assess patient characteristics: - indication for analgesia - age, sex, weight - culture - vital signs - allergies/ADRs - opioid tolerance - respiratory status - renal/hepatic function - other medical co-morbidities - mental state - other Rx - availability of oral/rectal routes

26 WHO Analgesic Ladder (ideally fro chronic pain) Level 1: Non opioid/adjuvant (paracetamol; NSAIDs; amitriptyline; local anaesthetics) Level 2: Weak opioid + non-opioid Level 3: Strong opioid +/- non-opioid/adjuvant NOT ACCEPTED- Use Multimodal Analgesia

27 DRUGS PAIN TYPE Nociceptive e.g. fracture Neuropathic eg neuralgia Inflammatory e.g. rheumatoid arthritis ParacetamolEffective when taken regularly at max. dose Less effectiveEffective, but not anti-inflammatory OpioidsEffectiveMay be effective (agent + dose) May be effective (depends on dose) NSAIDsEffectiveNot effectiveEffective TCAs, parenteral, local anaesthetics antiepileptic Rarely used (clonidine may be effective as adjunct) May be effective Rarely used (may be effective as adjunct) Adapted from Table 3-1, Australian Medicines Handbook

28 NSAIDs- Adverse Effects Side effectsCautions hypersensitivity/allergy GI (GORD/PUD) platelet inhibition sodium retention, oedema renal toxicity hepatic toxicity

29 NSAIDs- Adverse Effects Side effectsCautions hypersensitivity/allergy - asthma GI (GORD/PUD) - GI bleeding/ulceration platelet inhibition - coagulation disorders - warfarin therapy sodium retention, oedema - hypertension - cardiac failure - ACEI/ARA/diuretics renal toxicity - renal impairment - gentamicin therapy hepatic toxicity - hepatic impairment

30 NSAIDs – Caution! Major cause of ADEs and hospital admissions  use lowest effective dose for shortest possible time  use paracetamol as alternative or to reduce NSAID dose  COX-2 inhibitors - similar adverse effects to non-selective - increase risk of thrombotic events (stroke; MI)!  little difference in efficacy between NSAIDs  avoid aspirin < 18 yrs in viral illness (Reye’s syndrome)  elderly - increased risk of adverse effects Continue only if effective. Avoid if possible!

31 Potential Adverse Effects of Opioids?

32  respiratory depression  sedation  nausea and vomiting  confusion  hypotension; bradycardia  pruritus  constipation / ∆ gut motility  urinary retention Opioids – Adverse Effects

33 Opioids – Precautions  hypotension, shock  concomitant CNS depression  impaired respiration /↓ respiratory reserve  elderly  hepatic impairment  renal impairment  epilepsy/recognised seizure risk  biliary colic or surgery  phaeochromocytoma

34 Regular vs PRN Analgesia  regular analgesia is better in setting of continuous pain  PRN only if pain intermittent and unpredictable  in most settings, pain is predictable  problems with using only PRN analgesia - dose prescribed by Dr/administered by nurse - patients don’t ask for medication  inadequate or infrequent dosing → unrelieved pain  keeping up with pain is easier than catching up with pain  prn dose = 1/6 →1/12 total regular daily dose

35 Key Messages  individualise analgesic therapy  choose analgesics judiciously  use multimodal analgesia  regular pain monitoring is critical to outcomes  regularly review and revise analgesic doses  adjust regular dose according to breakthrough usage  anticipate and manage analgesic-associated adverse events  avoid NSAIDs – major cause of morbidity/mortality!  avoid tramadol, dextropropoxyphene, pethidine

36 Electrolyte Objectives Fluid requirements Common error traps Electrolyte requirements Key messages for safe electrolyte prescribing

37 Maintenance Fluid for “Standard” Patient – 70 kg – euvolaemic – no electrolyte derangements – not septic – normal cardiac and renal function – no additional ongoing fluid losses

38 SodiumGlucosePotassium Daily Requirement2 mmol/kg>100G1 mmol/kg 0.9% NaCl 1L (Normal Saline) +/- 20/40 mmol KCl/l 150 mmol0 0, 20 or 40 mmol 4% glucose & 0.18% NaCl 1L 30 mmol40G0 3.3% glucose & 0.3% NaCl +/- 20/40 mmol KCl 1L 50 mmol33G 0, 20 or 40 mmol

39 Risks of Having IV Line Infection – Time and effort to re-site every 48 hours Immobility Thrombophlebitis Direct costs of consumables Overdosing of fluids and electrolytes

40 Key Messages IV Fluid Ordering Supply orally if possible Assess current fluid status - wet / dry / ‘just right’? - how do you tell? Review fluid balance chart Assess ongoing requirements and losses Reassess fluid status at least daily

41 Potassium What is normal? Where do you lose it from? How much do you need? How can you replace it? Routes of administration? How fast can you replace it? Quantities? What goes wrong?

42 Potassium Normal serum K + = mmol/L Daily requirement = 1 mmol/kg Dietary K + < 25 mmol (1gram)/day leads to hypokalaemia Is magnesium low (< 0.5 mmol/L)? (makes it difficult to correct potassium)

43 Causes of Hypokalaemia Potential sites for K + loss - urine; faeces; drain sites; vomitus Intracellular shifts - insulin - β adrenoceptor agonists - caffeine - hyperthyroidism - correction of acidosis Increased external losses - Drugs that promote renal K + excretion  loop diuretics (eg frusemide)  aldosterone; thiazides; penicillins

44 Potassium Replacement There is no single way to correct potassium  serum K + of 0.3 mmol/L = overall deficiency  100 mmol K + (but extremely variable) Replace with oral supplements where possible Ideally, correction of potassium should occur over a period of days Account for deficit + ongoing normal requirements

45 Case Study - Mr KCl 72 y.o. ♂ Med Hx: hypertension, heart failure Rx: frusemide 80mg mane; lisinopril 10mg mane; amlodipine 10mg mane Admitted for elective TKR Pre-op serum potassium: 2.9 mmol/L Registrar: - “Give him some IV KCl and fluids pre-op” - suggests 40 mmol in 100mL N Sal over 60 min - What happened?

46 Potassium Administration In non critical care cases, Should NOT give KCL > 10 mmol/hour WITHOUT a pump With a pump max. rate = 20 mmol/hour Concentrations > 40 mmol/L: risk causing thrombophlebitis, pain and loss of IV site If via central line, concentration NOT a concern, but RATE is!

47 Causes of Hyperkalaemia ↓ K + excretion (renal insufficiency) ↑ K + intake (but rapid K + excretion 2 o to ↑ intake) K + release from cells Metabolic acidoses Medications Hypoaldosteronism/resistance to aldosterone

48 Managing Hyperkalaemia – What are your aims? – What are the risks? – What do you do? – How do you do it?

49 Cardiovascular Protection Calcium Gluconate by slow IV push – decreases membrane excitability – 10 mL of 10% calcium gluconate (2.2 mmol) – onset 2-5 minutes, lasts up to an hour – can repeat if no ∆ ECG after 5-10 minutes

50 Shift Intravascular → Intracellular Insulin - 10 units insulin in 50 mL of 50% glucose - via syringe or free running drip - onset minutes, lasts 1-3 hours - ↓ plasma K + by mmol/L Nebulised salbutamol - 5 mg - onset within 30 minutes, lasts 2-4 hours - ↓ plasma K + by mmol/L

51 Removing Excess Potassium Resonium ® A (sodium polystyrene sulfonate) - promotes exchange of Na + for K + in the GIT - 30g orally or 60g enema mixed with glucose - onset within 2 hours, peak effect at 6 hours - 1 gram binds 1 mmol K + and releases 2-3 mmol Na + - generally lowers plasma K + by mmol/L - can give up to 4 doses per day (as per levels) Haemodialysis - severe life-threatening hyperkalaemia unresponsive to more conservative measures

52 Sodium Replacement Consider - ? over filling (heart, renal, liver failure) - ? over diuresis - ? SIADH – SSRIs; TCAs; carbamazepine Replace Na + gradually (↑ plasma Na + by ≤ 10 mmol/L/day) Na+ required to ↑ plasma Na + by 10 mmol/L: [0.6 * total body weight (kg)] * 10 = x mmol/L Na + NEVER attempt to replace sodium with hypertonic saline! - IRREVERSIBLE osmotic demyelination of CNS (several cases in QLD in recent years)

53 Magnesium Indications - hypomagnesaemia - post MI - antiarrythmic - acute asthma - pre-eclampsia Oral - limited value (laxative) Be aware of IV rate - vasodilator!

54 Key Messages Use oral route for electrolytes if possible Significant patient harm 2° to rapid/concentrated KCl K + reduction - protect heart (short and long term) NO place for hypertonic saline – demyelenitaion risk Magnesium used for hypertension

55 Questions?


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