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Case7Revision- Ageing,Frailty& Polypharmacy • Describe the different regions of the vertebral column and identify the anatomical features of a typical vertebra • Describe the functional anatomy of the upper limb • Delineate the normal structure, growth, and biochemistry of a long bone • Outline the mechanisms involved in calcium homeostasis • Define how skeletal structures are maintained through bone remodelling and the mechanisms through which bone fractures are repaired • Describe the age-related decline in physical function and the age–associated atrophic changes in bone • Describe the hormonal changes associated with menopause, and the consequent changes in oestrogen- dependent tissues • Define the risk factors for osteoporosis, and the benefits of physical activity in the prevention and management of this condition • Explain the principles of hormone replacement therapy (HRT) and contextualise the associated risks • Describe frailty and state the associated risks ILOs • Describe the components of the skin including the dermis, epidermis, and epidermal appendages • Detail the processes by which wounds heal by both primary and secondary intention • Define the control of infection in a clinical environment. Understand the risks of MRSA infection and its management. • Understand the principles of sepsis and how this condition is prevented and treated. • Define the indications, contraindications, and side-effects of steroid treatment • Explain how aging impacts on the body’s handling of drugs • Recognise the issues of multiple morbidity and polypharmacy • Describe societal influences on perceptions of age • Apply the biopsychosocial model to explain the concept of successful ageing • Give examples of circumstances where it might be acceptable and/or necessary to breach a patient’s Confidentiality • Revisit the risk of breast cancer Calcium HomeostasisBoneRemodelling BoneFractureRepair • Bone fracturesrepairthrough bonehealing • 1.Haemostasis(Blood Clotting&Inflammation) 4.Hard CallusFormation (Week 3–6) • Immediately afterthe fracture,bloodvesselsinthebone& surrounding Ossification occurs, where the soft callus isgradually replacedbyhard, tissues rupture,causingbleeding bone-like tissue Thecartilage is convertedinto wovenbone throughthe activity • The body responds byforminga blood clotaroundthe fracture site,which helpsstopthe bleeding& actsasafoundationforthehealing process of osteoblasts(bone-forming cells) • Inflammation occursasWBCsareattractedtothe injury site toclean up A hard callusforms aroundthe fracture, providing more stability tothe debris,bacteria,& damagedtissue bone • Inflammatorycells also releaseGFsthat promote healing This new bone isnotyetasstrong orasorganisedasnormal bone • 2.InflammatoryPhase (Day 1–7) 5.Bone Remodelling (Months to Years) • The body initiatesinflammationaroundthe fracture,& thebodyworksto Over the long term, the newlyformed bone continues tomature & stabilise the break strengthen • The clotthat formsaroundthe fracture site isgradually replaced Thewovenbone isreplacedby lamellarbone, whichisstronger& more by granulationtissue,whichcontainsbloodvessels,collagenetc. structured • Osteoclasts(resorbbone)begintoremovedeadbonetissue Osteoclasts continue to remodelthe bone,reshaping it& removing any • Thisphase helpssetthe stagefortheformationofnew bone excess material • 3.SoftCallusFormation(Week1–3) Osteoblasts laydown new bone inthe proper orientationtorestorethe bone'soriginal shape &function • The body startstobuildasoft callusof cartilage &fibroustissue aroundthe Eventually, the boneregainsitsoriginal strengthandstructure, thoughit brokenboneends may take severalmonths toyears to complete this phase, depending on • Thissoftcallusbridges the gapbetweenthebrokenpiecesof bone the severity of thefracture • Chondrocytes(cartilage-producingcells) form acartilagematrix &fibroblastslaydowncollagenfibres • Thissoftcallusstabilises the fracturebutisnot strongenough tobear weight Age-RelatedAtrophicChangestoBones • Decreased Bone Density (Osteopenia & Osteoporosis) • Reduced Bone Mineralisation • Loses calcium & other minerals that give it strength & density • This makes bones morebrittle& susceptible to fractures • This declinein mineralisation can occur even beforesignificant boneloss, weakening thebones even when bone density hasn'tdecreased dramatically • Changes in Bone Architecture • Trabecular bone (spongy bone)in the vertebrae becomes thinner & more porous, increasing therisk of fractures • Thecorticalbone (thehard outer layer)also becomes thinner,reducing the bone's strength • Thetrabecular architecture loses its interconnectivity,leading to a weakening ofthe bone's abilityto withstand stress & weight-bearing forces • Decreased Bone Formation • Therate of bone formation byosteoblastsdecreases, meaning bones repair themselves less efficiently • This declineleads to slower recovery from fractures & a lower capacity for remodelling bones • This slower bone turnover increases therisk of fractures becausedamaged bone is not quickly replaced with new,stronger tissue • ImpairedBone Remodelling • Thebalance between osteoclasts & osteoblastsshifts,withosteoclast activity (bone resorption) increasing & osteoblast activity (bone formation) decreasing • This imbalance leads to boneloss & reduced bone strength • Changes in Collagen Composition • Thecollagen matrixin bone (provides flexibility & resilience) becomes altered with aging • The collagen fibres become stiffer & less organised, making bones more brittle &less able to absorb shocks,increasing the risk of fractures • Jointand Cartilage Changes • Cartilagemaybecomethinner & less elastic,leading to joint pain,stiffness,& conditions like OA, which can indirectlyaffect bone health • Theloss of cartilage leads to moredirect contact between bones in the joints,which can increase wear & tear on the bones &lead to further degeneration • Hormonal Changes • Oestrogen: drop after menopauseaccelerates bone loss;normally helps maintain bone densitybyinhibiting bone resorption, soits decrease leads to more bone breakdown • Testosterone:gradual decline contributes to bone loss • PTH:elevated levels can stimulate osteoclast activity,promoting boneresorption & further decreasing bone mass • Vitamin D: ageing reduces the skin's ability to synthesise vitamin D from sunlight,which affects calcium absorption from theintestines, leading to weakened bones • IncreasedRisk of Fractures • Especially in the spine, hips, & wrists • Vertebralfractures areespeciallycommon dueto the loss of trabecular bone& the decreased structuralintegrity of vertebrae • Hip fractures areconcerning dueto significant morbidity& mortality HormonalChangesinMenopause • Menopause- permanent • Number in responsivenessof last menstrualperiod, no ovarian follicles declines after40 periods for12 months, • Oestrogen & Inhibin B secretion is meanage 51 reduced as aresult • Nofurther productionof • This reduces thenegativefeedback oestrogen& progesterone on GnRH & FSH • Iatrogenic menopause- surgery(removalof • FSH levels increase ovaries), radio& chemo • Leftover follicles secrete oestrogen (damagetoovarian (fluctuating,erratic levels) tissue) • When thereareno responsive • Perimenopause- from follicles, negative feedback is symptoms topostopausal disruptedthereforeFSH levels menopause;periods occur aftera coupleof remain high; LH also increases due months, gradualprocess to disruption ovarianfunctionover • Ovarian stromal cells synthesis time) androgens which aromatise to • Prematuremenopause- oestrogen in adipose tissue <40 (oestrome, lessactive than oestrodial producedin ovaries) Usingthisinformation, howwouldyoudiagnosemenopause by investigations? • Osteomalacia- loss ofbonemineral • Osteomyelitis- infectionofbone • Osteoarthritis- diseaseofjoints • Oconnectivetissues ofentirebone substance &non-mineralised • Fractures ofnon-traumatic originaresustained • Windividualofsame sex& Z score- same sex &age)re(healthy • Osteopenia- 1-2.5 SD belownormalhealthycontrol • Riskfactors- Osteoporosis-Risk • Previous fragilityfracture • Currentuseor frequentrecent useoforalor systemic glucocorticoid Factors • Historyoffalls • Familyhistoryofhipfracture • Other causes ofsecondaryosteoporosis- • Hypogonadismineither sex including lowtestosteronein men&prematuremenopauseinwomen • Endocrine conditions, including DM, Cushing's disease, hyperthyroidism • Ccoeliacdisease& chronicpancreatitison, including IBD, • RA & other inflammatory arthropathies. • LowBMI(<18.5kg/m²) • Smoking • Alcoholintake>14units/week • 1.Improved BoneDensity • Weight-bearingexercises,suchaswalking,jogging,dancing, andresistance training,stimulate bone formationand canhelpslow orevenpartially reverse bone loss.These typesof exercisesput stressonbones, whichsignalsthebody toproducemorebone-formingcells,promoting boneremodelling. • Strengthtrainingwithweightsorresistance bands strengthensthe musclessurroundingbones andincreases the load onbones,furtherenhancingbone density,particularly in the spine,hips,andwrists. • 2.Increased BoneStrength • IncreasesBMD, particularly thespine,hips,and legs. Asbonesadapttothe physical stressesplaced onthem duringexercise,they become denserandmore resistant tofractures. • Exercisesthat involveimpact(e.g.,jumpingorrunning)and muscle strengthening(e.g.,weightlifting) Osteoporosis- encouragebonesto rebuildandgrow strongerovertime. • 3.Enhanced Balanceand Coordination Benefitsof • Balanceand flexibilityexercises(such as tai chi oryoga),helpsimprove posture,balance,andcoordination. Thisreducesthe riskoffalls,a leading cause of fracturesinpeoplewithosteoporosis. • Strengthening exercisesforthe lowerbodyandcore musclescan improve stability andreducethe likelihood of falling,important for brittlebones. Exercise • 4.Pain Reduction • Regularphysicalactivity canhelpalleviate pain fromosteoporosisby increasing muscle strengthandjoint flexibility,thereby reducingthe strainonaffectedbones. • Exercisecanalsohelpincreasebloodflowthusdelivery of nutrientsto bonesandtissues,supportinghealing andreducing discomfort. • 5.Improved Posture and SpineAlignment • Weight-bearingand strengtheningexercises canenhance spinal alignment • Overtime,osteoporosiscancause the spine to curve,leadingtokyphosis • Exercisesthat strengthenthe core andbackmuscleshelpsupportthe spine, preventingfurtherdeformities andimprovingposture.• 6. Reduced Risk of Further Bone Loss • progression of osteoporosisesistance activities stimulate the bone remodelling process tomaintain bone densityand slow down the • 7. ImprovedOverallHealth and Wellbeing • Increased muscle strength, improved cardiovascularfitness, and enhancedflexibility • Thesebenefits contribute to greater mobility,independence, and ahigherqualityof life for people living with osteoporosis. • Manage otherhealthconditionsassociated with osteoporosis,such as arthritis,diabetes, and heart disease • Reducestress, promote bettersleep,and improve mood • 8. Better Long-Term Functionality • E.g. theabilityto perform daily activities likewalking,climbing stairs,orcarrying groceries • By maintaining muscle mass and strength, peoplecan stay moreindependent and avoid complications associated with immobility. • 9. IncreasedFlexibility • Stretchingexercises and activities likeyogacan increase theflexibilityof themuscles and joints surroundingthebones to improve mobility, reduce stiffness,and lowerthe risk ofinjury. • 10.Support for MentalHealth • Reduceanxiety, depression, and feelings ofhelplessness that sometimes accompany chronic conditions like osteoporosis • Releasesendorphins (the body's natural mood enhancers), contributing to improved mental and emotional wellbeing • Oestrogen’sroles- • Increasesalkalinephosphotase expressionwhichisa markerof osteoblastdifferentiation • Increasescollage typeI synthesiswhichisthe maincollageninbone • Stimulatesgrowth factorsynthesissuch asIGF 1,TGFB&BMP’s whichare allimportant forcontrollingcell division&differentiation • Regulatesosteoblast proliferationthereforeosteoblastsmultiplyand mature • Stimulatesexpressionof VDRwhichisa receptorfor1,25 dihydroxy vitamin D3 Osteoporosis • Increasesapoptosisofosteoclasts • Suppressesosteoclast differentiationwhichpreventsosteoclast precursorscomingtogether(reside inbone marrow)tomature &Oestogren osteoclasts • Actsonosteoclastsvia osteoblasts(IL6,RANK/RANKL,OPG) • Oestrogen promotessynthesisofosteoprotegrin whichbindsto RANKL, preventingRANKLfrombindingto RANKtherefore osteoclastsdon’t differentiate;aspost menopausal women don’t haveoestrogen,osteoclastactivityisincreasedwhichchewsbone • Fallingoestrogenisassociatedwithincreased osteoclastsbut bone sectionsfromwomenwithosteoporosisshowsproblemswith osteoblasts(fewofthem) andfewosteoclasts • Ingeneral,asyouage, osteoblastsarenolongerable tocatchup with the activity of osteoclasts;menopause causessuddenincrease in osteoclast activitywhichacceleratesthe process • HRT- hormonereplacementtherapy • ashot flashes, night sweats, andvaginaldryness • fracturesinpostmenopausal womendreducetherisk of • Whileit has benefits,it mayalsoincreasetherisk ofcertain womenwithspecificrisk factorsnusedlong-termorin • Replacement oestrogens–oestradiol & conjugatedequine HRT oestrogen • Replacement progesterone- progesterone & norethisterone • Givenalongside oestrogentoprotect endometriumas oestrogencanincreasetherisk ofendometrial hyperplasia-> endometrialcancer • Benefits- • Oestrogenis mosteffectiveforvasomotor symptoms • Moodor sleepdisturbances • Urogenitalatrophy • Osteoporosis- reduces fragilityfractures,undertaken withweightbearing exercises, calcium,vitaminD, smoking cessation& reductionofalcoholRisksofHRT • 1. IncreasedRisk ofBreast Cancer • Especially combined HRT (oestrogen &progestin) • The risk increases with the duration of use,particularly if HRT is taken forseveral years • Oestrogen alone (used in women who havehad a hysterectomy)appears to carrya lowerrisk of breast cancer,but some studies haveshown an increase in risk with LT use • 2. IncreasedRisk of VTE • Particularlyoral oestrogen • Including DVT &PE • Higherrisk with otherrisk factors forblood clots,such as obesity,a history of clotting disorders, orsmoking • Lowerrisk with transdermal HRT (patches orgels),as these methods bypass the liverand haveless impact on clotting factors • 3. IncreasedRisk ofStroke • Combined HRT • Especiallyin older women orthose with other risk factors such as HTN or smoking • Lowerrisk in women who begin HRTat ayoungerageand use it fora short period • 4. IncreasedRisk ofHeart Disease • CV risk, particularly when started >60y/o orthose with existing heart disease • Combined HRTcan increasetherisk of heart attack andstroke • <60y/o orwithin 10 years ofmenopause, the risks might be lower,and HRTmay even provide some CV protection when started early• 5. EndometrialCancer (in womenwith a uterus) • For women who stillhavea uterus, oestrogen only • Oestrogen alone stimulates the growth ofthe uterinelining • Adding progestin helps protect the uterus and reducethe risk of endometrialcancer • Oestrogen + progestin combination -> increased risk of breast cancer • 6. Gallbladder Disease • Especially when taken orally • Increased risk of gallstones andgallbladder disease • Dueto changes in the liver’s processing of cholesterol and bile salts, which can lead to theformation of gallstones • 7. Possible Cognitive Decline • LTuse, particularly in older women,may be associated with cognitive decline and an increased risk of dementia,especiallyifHRT is started >65y/o • May be neuroprotective if started early in menopause • 8. Mood Changes andDepression • Can alleviate menopausalsymptoms like mood swings and irritability • Insome cases, it may cause mood changes,anxiety,ordepression, particularly true for women who have a history of mood disorders • 9. BreastTendernessand Other Hormonal Side Effects • Sideeffects- breast tenderness, bloating, nausea,headaches, and irregular bleeding • These symptoms may subside over time but can bebothersome, especially during theinitiation of therapy • 10. Risk of OvarianCancer • Slightly increased riskwith LT use • However, the risk is smalland is more commonly associated with the useofHRT in women who have not had a hysterectomy Healthcarecrisisprovoked Any rapid change to one’sfunctional abilitycanindicateillness Frailty &itsRisks • Frailty-state of increasedvulnerabilitytopoor resolution of homeostasisafterastressor event, whichincreases therisk of adverseoutcomes • i.e. morelikelythatsomethingbadwillhappen toyou,whenitdoes,yourbodywon’trespond as effectively,andthentheoutcome is worse • Outcomes are worse- • Morefalls • Higherrates of hospitalisation • Higherrates of care home admission • Highermortalitye,g.Pneumonia,hipfractures WoundHealing • 3 phases- • Inflammatoryphase: • Formationofbloodclot • Haemostasis (stopping ofblood) occurstoallowfor vascular dilationtoinitiate inflammation • This leads toa rise inexudate levels (mass of cells and fluids thathas seeped outofblood vessels) • Thesurrounding skinneedstobe monitoredfor signs of maceration(softening towetting ofthe skinowing toretentionofexcessive moisture) • Proliferative phase: • Woundisrebuiltwithnew granulationtissue (connective tissue- collagenand extracellularmatrix- and bloodvessels) • Healthygranulation tissue occurs whenfibroblasts receive sufficient levels of oxygenand nutrients suppliedby theblood vessels, isgranularandunevenin texture,doesn’t bleedeasily, and ispink/ redincolour • Thecolourandconditionofgranulationtissue isoftenanindicator of how the woundis healing • Dark granulation tissue- poorperfusion, ischaemia and/orinfection • Epithelialcells finallyresurface the wound- epithelialisation • Maturation phase: • Occurs once thewouldhas closed • Involves remodelling ofthe collagen from type iiito type i • Cellularactivity reduces andthe numberofblood vessels in thewoundedarea decreases Sepsis • Sepsis- life-threatening organ dysfunction caused bya dysregulated host response to an infection • Immune mechanisms designed to fight infection activate pro- inflammatory responseswhich lead to cellular & tissue damage & anti- inflammatory responseswhich lead to immunosuppression • Septicshock- more severeform of sepsis, circulatory,cellular& metabolic abnormalities are associated with a greaterrisk of mortalitythan with sepsis alone • QuickSOFA score- • RR >22 • Altered mentation • SBP <100mmHg • ≥2- heightened risk of mortality • Sepsis Six Bundle (<1 hour)- • ‘Give 3,take 3’ • Give O2(>94% target,88-92% ifretaining CO2,in what condition?) • Give broad spectrum ABX • Give IV fluids (500ml crystalloids within 15 minute) • Take blood cultures • Measureserum lactate • Measureaccurately hourlyOU • Infection prevention- • Prophylactic useofABX, but limited evidenceasit usually only benefitscertaingroupsi.e. surgical prophylaxis • Broad spectrum pathogens- Infection decontamination, PPE, Control management of sharps, waste disposal,laundry • Isolation- is beneficial, but due to psychological impact, may not alwaysbetheoption • Methicillin-resistant staphylococcusaureus • Usually livesonintactskin,gut, nose harmlessly(1/3population),but deeperpenetration causesharm • DevelopedresistancetomanyABX • Cancause awidevarietyof infectionsfrommildtolifethreatening- • fasciitisttissue infectionssuchasboils,folliculitis,impetigo,cellulitis,necrotising • UTIs • Pneumonia &bronchiectasis • Joint& bone infections-osteomyelitis& septic arthritis • Sepsis& toxic shocksyndrome • Infectiveendocarditis MRSA-Risks& • Riskfactors- • Beinghospitalised, invasive medical device,residing inLTcare facility (HA-MRSA) • Contactsports,crowded,unsanitary areas, HIV, illicit injecteddrugs (ca-MRSA) Management • Management- • Urgent assessment insecondary care if suspectedorconfirmedMRSA &clinical features ofsevere orcomplicatedinfection,orsurgical interventionrequired • Discusswithmicrobiology fortreatmentoptions • RoutinePOortopical ABXnot advised • Followup tomonitorsigns ofcomplications& ensureresolving • asymptomaticcarriersevice orincare home,canconsiderdecolonisationin • UTIs-doxycycline,trimethoprim,ciprofloxacin,co-trimoxazole • ComplicatedUTI-glycopeptide • (BNFforotherinfections) • Synthetic versionsof hormonesproducedbythe adrenal glands • Inhibit immune system-useful totreat autoimmuneconditionssuchaslupusorRA • Suppressinflammation-reducesredness& swelling,useful forinflammatory conditionse.g.asthma, eczema,temporal arteritis • Inhibit vasodilation&increase vascular permeability • Canleadto an alteredfluidretentionatasiteof tissuedamagewherefluidcan’t reachit soreduces swelling • Rescuesnumberof circulating lymphocytes&inhibitsemigrationtodamagedtissue whichalso reducesswelling • Inhibitscytokine expressione.g.IL-2&TNF • Inhibitsproductionof phospholipase whichpreventsformationof Arachidonicacid& inflammatory mediators • Contraindications- • Untreatedsystemic infection • Cautiouslyused inDM,HTN,hepatic impairment Steroids • Anticoagulants,anticonvulsants,DM meds,HIV meds,NSAIDs(interactions) • Mineralocorticoidside effects(e.g.progesterone,deoxycorticosterone)- • HTN • Na+retention • Waterretention • K+loss • Ca2+ loss • Glucocorticoid side effects(e.g.beclamethasone,hydrocortisone,prednisolone, budesonide etc.)- • Diabetes • Osteoporosis • Highdoses-avascular necrosisof thefemoral head • Musclewasting(proximal myopathy) • Pepticulceration&perforation(weaklink) • Psychiatricreactions Ageing&HandlingofDrugsbythe Body • Pharmacodynamics- whatthedrugdoestoyourbody • Absorption- • Some reductioninsecretionofgastric acid& enzymesinGIT • Reducestotalsurface area (reduction in villi) • Slowingofgastric emptying/motility • Potentialdecrease inabsorption ofdrugs • Overall- smallchanges • Distribution- • Reducedmuscle mass due tophysical inactivity • Reducedtotalbody water • Increasedbody fat • Reducedbody mass • Lipid soluble drugs- greatervolume ofdistribution, whichcangradually accumulate infat&braintissue e.g. benzodiazepines thereforethe effectsareprolonged • Water soluble drugs- smaller volume of distribution, can lead to higherplasma/serumlevels; toxic if drughasa narrow therapeuticindex • Metabolism- • Reducedhepaticvolume& bloodflow (~40%) • Reducedfirst pass metabolismwhichincreasesthe bioavailability ofsome drugsmetabolisedby theliver • Smoking, alcohol, co-existingdisease &somedrugscanfurtherimpair liverfunctions • Overall- smallchanges Increased pharmacodynamic sensitivity to many drugs, pharmacological effects,susceptibilityto ADRs • Excretion- • Renalfunctionreduceswithage(reducedeGFRby 1ml/min/year>40y/o) Increased risk of toxicity- Gastrotoxicity- NSAIDs • Reducedby coexisting chronic conditionssuchas diabetes, CCF &acute illnesses suchasUTI &dehydration Neurotoxicity- opioids/drugs that can pass through theBBB • Reducedclearance ofdrugs whichareexcretedvia filtration atthe kidney e.g. digoxinoractively secreted by the renal tubules Nephrotoxicity- gentamicin suchas penicillin Vasodilation- BPmeds -> orthostatic HTN • Canresultindrug&metabolite accumulation&toxicity Need to lower doses in the elderlydue to these effects • May needdose-reduction for renally-cleareddrugs • Overall- significantchanges Polypharmacy • Use of multiple medications bya patient (≥5) • Pros: • Medicinesuseoptimised • Eachmedicine achievesitsintended benefit • No ADRsorinteractions • Cons: • Multiple medicines prescribedinappropriately • Intended benefit of eachmedicine isn’tachieved • ADRs&interactions • Impact in olderpeople- • Increasingthe numberof drugsincreasestheriskof ADRs/side effects&drug-druginteractions • Effects of ADRs- • Unnecessary investigations • Treatment delays • Longerhospital stays • Negative impact onQoL • Increasing the numberofmedications can lead to problems with adherence as theycan find it difficult to rememberto takethem • Thisis aggravatedbyvisual& cognitive impairments • Leadstoincreaseddependence onothersMCQs• What hormoneissignificantly elevated inmenopause? • A)LH • B) FSH • C)Oestrogen • D) Progesterone • E)AMH • What does progesterone only therapy increase the riskof? • A)Leukaemia • B) Cervicalcancer • C)Myeloma • D) Breast cancer • E)Ovariancancer• Which of the following drugs can increase therisk monitored andcontrolled?rly patientsif not • A) Co-codomol • B) Gabapentin • C)NSAIDs • D) Bendroflumethiazide • E) Gentamicin • Whatform of oestrogen is producedduring menopause byadipose tissue? • A) Oestrodiol • B) Oestrogen • C)Oestrome • D) Oestrone • E) Oestriol• A 64-year-old man is admitted to the emergency department as his wife is concerned that he is becomingconfused following a recent bad chest infection. She reports that he has not improved after a course of amoxicillin. On examination,his respiratory rate is 30/min,blood pressure 88/60 mmHg, heart rate 120/min. Crackles are noted on the right side of his chest. What is the most appropriate fluid therapy to give? • A)20ml/kgstat • B) 30ml/kg stat • C)500ml stat • D) 20ml/kg over1 hour • E)10ml/kgover 1 hourQuestions?Feedback • https://app.medall.org/feedbac flow?keyword=58859f2c66d4d 7598fe3eafe&organisation=ma nchester-meded