A Potpourri of Problems An interesting case in General Medicine

A Potpourri of Problems: An interesting case in General Medicine Kirsten Murray Advanced Trainee in General Medicine John Hunter Hospital Hunter New England Health Mrs EK • 80 year old female • German born. In Australia for 50 years • Lives with 2nd Husband in own home •Independent in self care •mobilises with A-frame indoors •wheelchair outdoors or in community •home modifications in place Mrs EK • Devoted husband who drives, cooks, cleans and does all home duties • Pt occasionally cooked sitting on bar stool • Shop together once a week • Visit local club for a meal once a week Mrs EK • Pt self-administered medications from packets • Husband occasionally assisted • Apparently good compliance Presenting Complaint • Severe chronic diarrhoea • progressive over six months Chronic Active Medical Problems • 1. Aortic Valve Replacement • 2. Angiodysplasia • 3. Chronic Leg Ulcers Aortic Valve replacement 1994 • • • • Mixed aortic valve disease Medtronic Hall 21mm prosthetic valve warfarinised - target INR 2.5 Recent trans-thoracic echo June 2004: – normal ejection fraction – normal valve function with periprosthetic aortic regurgitation Chronic Active Medical Problems • 1. Aortic Valve Replacement • 2. Angiodysplasia • 3. Chronic Leg Ulcers Angiodysplasia • Haematemesis and malaena 2002 and 2003 • Endoscopy: – 2 small angiodysplastic lesions (<5mm) at gastro-oesophageal junction and greater curve – adrenalin injection and gold probe diathermy in 2002 – proton pump inhibitor – intermittent anaemia, requiring transfusion when INR >2.5 Chronic Active Medical Problems • 1. Aortic Valve Replacement • 2. Angiodysplasia • 3. Chronic Leg Ulcers Chronic Leg Ulcers • • • • Chronic, for years four on left, one on right pain on walking --> wheelchair extensively investigated Investigations • ANA 1:80 speckled • C3 low, C4 normal • cryoglobulin + • • • • ANCA negative ENA negative AFB negative Fungal Biopsy negative Investigations • Duplex 2/04 – right peroneal and posterior tibial artery occlusion – Biopsy 4/04 – nil malignancy – some calcium but not calciphyllaxis Treatments • Prednisone trial - no improvement--> stopped • Vac Dressings • Alprostadil infusion • left lumbar chemical sympathectomy (phenol) Inactive Problems • Ovarian Cancer 1982 – Hysterectomy and bilateral salpingo-oophorectomy – no documented recurrence • Tuberculosis in 1940’s with calcified lymph notes and granuloma in chest on CT • Partial thyroidectomy for goitre, aged 27 • Polymyalgia rheumatica 2001. On prednisone x months • Right renal calculus 2001 - haematuria Inactive Problems • Ischaemic heart disease – previous angiogram 2001 showed LAD disease – treated with nicorandil and atenolol – asymptomatic • Hypercholesterolaemia - Cholesterol 8.2 • Hypertension >10 years requiring multiple drugs • Primary hyperparathyroidism -->parathyroidectomy 1996 • osteoporosis --> bone fractures Medications on admission • • • • • • • • Warfarin 2mg daily fosinopril 20 mg daily spironolactone 25 mg daily nicorandil 20mg bd atenolol 50mg daily simvastatin 20 mg daily caltrate 600mg daily alendronate SR 70mg weekly Creatinine Clearance • Usual creatinine around 80 • weight 60kg • Calculated creatinine clearance via CockcroftGault formula = 46ml/min Drug Intolerances • Allergy to sticking plasters • Intolerant to: – verapamil - ankle swelling – thiazides • Light ex-smoker 20 pyh. Nil x 15 yrs • Family history: nil significant Recent Admission April 04 • Diarrhoea, nausea, vomiting, abdominal pain • Elevated amylase and lipase – amylase 309 (RR 0 - 95) – lipase 662 (RR 665) • Upper abdominal ultrasound - gallstones, nil else • + Faecal occult blood • Clostridium difficile toxin negative April 04 admission • Empiric treatment with metronidazole • Improved and discharged • Dx: ? viral gastroenteritis Presenting Complaint • • • • • 6 months of diarrhoea loose, brown, watery no blood nocturnal initially 2-3 x per night Last two months….... • • • • • nocturnal, 3-6 x per night associated lower abdominal crampy pain partial relief with opening of bowels precipitated by food weight loss of 15- 20 kg – usual weight 58 - 60 kg Last two weeks…. • • • • • Poor oral intake vomiting after many meals anorexic + + + extreme lethargy and weakness husband having difficulty caring for her Last two days…. • Eaten and drunk nothing • passed no urine • continued all medications including – spironolactone – fosinopril – warfarin Absence of: • • • • Back pain chest pain gynaecological symptoms fevers or night sweats • Denied sick contacts • Denied recent antibiotics On examination • • • • • Orientated but very drowsy Looked very ill Cachectic Afebrile Facial telangiectasiae • BP 105/58 (usual systolic 140) • PR 118 (beta-blocked) • RR 20 Sats 97% RA Cardiovascular examination • • • • • • Dry mucous membranes HS dual with 3/6 ESM, max. LLSE soft calves mild peripheral oedema leg ulcers no stigmata of infectious endocarditis Abdominal examination • Abdomen soft, non distended • moderate tenderness left side with no guarding • PR: empty, normal tone and no masses • U/A: requested but not documented Examination • Chest clear with mild reduction in air entry • no clubbing • breast examination normal • no lymphadenopathy Investigations • ECG - sinus rhythm • Partial LBBB (old) • CXR - old granuloma right mid zone • heart size upper limit of normal • bilateral apical pleural thickening and upper lobe scarring • AXR - localised ileus of the distal small bowel • extensive vascular calcification • Differential Diagnosis ?? Blood tests • Sodium Potassium Chloride Bicarb Urea Creatinine Anion Gap Ionised Ca Magnesium CRP Vitamin B12 137 5.5 105 16 22.4 201 23 1.10 0.63 253 395 H L H H H 136 - 144 3.4 – 4.8 98 - 108 24 - 30 3.5 – 7.2 60 – 100 7 -17 1.04 – 1.24 0.60 – 0.95 mmol/L < 11 mg/L 135 –600 pmol/L H Differential Diagnosis? Full Blood Count and Coagulation WCC 28.7 H Neutrophils 27.3 H Lymph 0.6 L Mono 0.9 H Hb 112 L Platelets 413 H MCV 86.9 APTT 60 H INR 5.2 H TT 13 ESR 42 Mild toxic changes on film 4.0 – 11.0 115 - 165 150 - 400 80 - 100 22 - 35 2.0 – 4.5 12 - 16 Diagnosis ? Other investigations • TSH 1.71 (RR 0.40 - 4.00) • Serum and urine IEPG : no monoclonal bands • LFT : albumin 28 > 24 > 21 » other LFT normal • Iron studies: Ferritin Iron TIBC Trans. Sat. 182 1 28 4 182 – 260 ug/L 10 – 27 umol/L 48 – 68 umol/L 15 – 50 % L L L Other Investigations Gliadin Ig A Gliadin Ig G Transglut. IgA ANA C-ANCA MPO Pr3 10 23 4 Positive Positive 2 1 < 10 EU < 42 EU < 20 EU 1:320 Speckled 1:10 “Uncertain significance” <6 U/ml <2 U/ml Wound Swab left leg • Profuse methicillin-sensitive staph. aureus • Scanty pseudomonas Faeces samples • • • WCC RCC Culture Nil Nil Negative Negative Negative • Giardia screening test • Cryptosporidium screening test Treatment and Progress • IVF resuscitation • warfarin withheld • • • • • Day 2: Good urine output and creatinine 201 -->117 Persisting severe diarrhoea INR 4.6 Gastrointestinal consult • Management of INR ?? Day 3 • • • • • Large spontaneous bleed from leg ulcers 500ml blood loss dizzy BP 98/36 PR 95 (beta-blocked) INR 5.8 Hb 99 Cr 104 Fevers to 38.3 degrees • Rx • 1 mg Vitamin K IV • Transfused 1 unit packed cells Day 4 • • • • Hb 92 INR 1.5 Clexane commenced Warfarin ceased Creatinine 104 --> 79 • Abdominal CT scan: – markedly dilated gall bladder – small gall bladder calculi – slight dilatation of intrahepatic ducts, common bile duct and pancreatic duct – atrophic pancreas. Granuloma in spleen else normal – slight reduction in kidney size else normal Day 5 • Clostridium difficile in stool culture – in 1st of 4 • Vancomycin commenced 125mg QID po Progress…. • Fevers ceased four days after commencing vancomycin • ERCP (with antibiotic cover) - NAD • possibility of need for placement noted in notes • GIT symptoms began to improve • Albumin 15 on day 7, now slowly improving Progress... • Continued improvement in GIT symptoms • Vancomycin reduced to 125mg BD from day 22 • Yakult BD commenced Progress • Albumin 21 • Gained weight to 60kg LMO clarification • Cephalexin 500mg po QID in September 2004 for left leg cellulitis • Also cephalexin in October 2003 In Summary….. • Chronic diarrhoea • acute renal failure – ongoing use of spironolactone and fosinopril • warfarinised – high INR’s – spontaneous bleed Clostridium difficile First Issue Clostridium difficile • Gram positive anaerobe • spore-forming • produces two exotoxins – A and B • Asymptomatic carriers – 5% of healthy adults – 20% elderly debilitated Pseudomembranous Colitis • Disruption of normal colonic flora • usual antibiotics – amp/amoxycillin – cephalosporins – clindamycin • focal areas of inflammation >>pseudomembrane Symptoms • 80% over 65, usually frail with comorbidities • symptoms commence usually first week but up to 6 weeks after therapy commences • crampy abdominal pain • profuse watery diarrhoea, sometimes bloody • fever • toxic dilatation and perforation • ileus Investigations • Faecal leukocytes common • hypoalbuminaemia (protein losing enteropathy) • Leukocytosis in blood • C.difficile toxin assay – 90% sensitivity – 99% specificity Treatment • • • • • • metronidazole 500mg TDS po or 250mg QID vancomycin 125mg QID po treat for 10 days response rate is 90 - 97% AVOID antiperistaltic agents discontinue implicated antibiotic if possible Other treatment considerations • Only metronidazole effective for IV therapy – not vancomycin • Indications for vancomycin – pregnancy and lactation – intolerance of metronidazole – failure of metronidazole treatment • Risk of vancomycin resistant eneterococci • ileus or toxic megacolon prevent drug reaching target site Precautions • May be transmitted within hospitals • good infection control - hands and surfaces • restricting use of antibiotics (especially clindamycin) Relapse • NOT related to antibiotic resistance • Recurrence of symptoms 3 - 21 days after antibiotics discontinued • 1/3 assays stay positive immediately after treatment • most respond to 2nd course of antibiotic for 10 days • ?reduced IgG antibodies to toxin A Renal Impairment 2nd Issue Renal Impairment • ACE inhibitors, NSAIDS and diuretics individually or in combination are implicated in over 50% of iatrogenic acute renal failure • “The triple whammy” – three simultaneous deleterious blows with compounded effect » M. Thomas; MJA 2000 ; 172 : 184-5 Haemodynamic changes in diminished “effective” volume • Compensatory mechanisms to preserve GFR: – 1. Local stretch receptors – vasodilatation of afferent arteriole – 2. Prostaglandins dilate afferent arterioles – 3. Angiotensin II –constriction of efferent arterioles Glomerular Function • Pre-glomerular arteriolar dilatation and post-glomerular arteriolar constriction preserve glomerular perfusion • normal GFR maintained Drugs • ACE inhibitor - prevents creation of angiotensin II • NSAIDS - inhibition of prostaglandin synthesis • spironolactone - aldosterone blocker • diuretics - promote volume loss Important points • Pt education to stop NSAIDS, ACEI and diuretics if unwell • stop them / withhold them in hospital 3rd issue Management of warfarin Day 1 5.2 Day 2 4.6 Day 3 5.8 Day 4 1.5 Day 5 1.2 Problems • Why did this happen? • How should this be managed? What Foods are Rich in Vitamin K ?? Vitamin K Content in Food FOOD Broccoli, cooked Lettuce, raw Parsley, raw Spinach, raw Cenovis Nature’s Own Centrum Blackmores SERVING 1 cup (chopped) 1 cup (shredded) 1 cup (chopped) 1 cup (chopped) Mega Multi Multivitamin VITAMIN K 420 mcg 118 mcg 324 mcg 120 mcg 0 mcg 0 mcg A – Z multivitamin 30 mcg BioACE 50 mcg Mrs EK • Usually ate salad and broccoli alternating days • usual warfarin dose 2mg • knew she should have INR if sick • last INR 2 months ago Consensus guidelines for warfarin reversal when no bleeding Australasian Society of Thrombosis and Haemostasis MJA 2004; 181 (9) : 492 -7 High INR but<5 INR 5 – 9 INR >9 Lower dose or Cease warfarin omit next dose and and consider why resume at lower dose when INR approaching therapeutic. If INR minimally elevated (up to 10%) , dose reduction may not be necessary If low bleeding risk, cease warfarin and give Vit K 2.5 – 5mg orally or 1mg IV. Measure INR in 6 – 12 hours, and restart when INR <5 If high bleeding If high risk of risk, give Vit K 1-2 bleeding, cease mg orally or 0.5 – warfarin and Vit K 1mg IV 1mg IV Measure INR within 24 hours. Resume at reduced dose when therapeutic Consider prothrombinexHT and FFP. Measure INR in 6 – 12 hours and restart with lower dose when INR<5 Australian Consensus guidelines: Risk factors for bleeding Age Cardiac Gastrointestinal >65 Uncontrolled hypertension History of GIT haemorrhage, active PUD, hepatic insufficiency Haematology/Oncology Platelets<50, platelet dysfunction, coagulation defect, underlying malignancy Neurologic History of stroke, cognitive or psychological impairment Alcohol Excessive intake Trauma Medications Recent trauma, history of falls Aspirin, NSAIDS, COX-II inhibitors SUMMARY: Important Points • Severe chronic diarrhoea – test for Clostridium difficile • Dehydrated patients need to stop ACEI and diuretics – pt education – hospital setting • INR’s affected by oral intake – pt education – watch INR’s closely The End