Decompensated chronic liver disease OHFP.indb 312 OHFP.indb 312 30/05/2014 16:18 30/05/2014 16:18 313 LIVER FAILURE Liver failure Worrying features Ascites, hepatic fl ap, altered mental state and jaundice are cardinal fe atures of decompensation in liver disease; also beware active bleeding, renal failure, iHR, dBP. Think about emergencies acute liver failure, decompensated chronic liver disease, hepatic e ncephalopathy; acute liver failure paracetamol overdose (b p495), viral hepatitis (A, B, C, E, CMV, EMV), pregnancy, medications (see below), toxins (eg poisonous mushrooms), vascula r (eg Budd \200\223Chiari), sepsis, Weil \200\231s disease, abscess; chronic liver failure alcohol, medications (see below), idiopathic, autoimmune, hepatitis (B D, C), malignancy, Wilson \200\231s disease, haemochromatosis, A1-antitrypsin defi ciency. Drug-induced hepatotoxicity1 may result in response to a large number of drugs, ranging fro m mild elevations in LFTs to fulminant hepatic failure. Paracetamol, NSAIDs, ACE inhibitors , erythromycin, fl uconazole and statins commonly cause hepatocellular injury (ALT >2x uppe r limit normal with normal/minimally iALP). Chlorpromazine, oestrogens, ciprofl oxacin, iso niazid, phenytoin, erythromycin and co-amoxiclav can all cause cholestasis (iALP, with or w ithout associ- ated hepatocellular damage). Always ask about recreational drugs (eg cocaine , mushrooms) and over the counter or herbal medications. 1 Useful review article available free at (cid:27)www.ncbi.nlm.nih.gov/pmc/articles/PMC2773872 Ask about tiredness, jaundice (+onset), abdo pain, drowsiness con- fusion, bruising, ble eding (skin, nose, bowel, urine), distension, ankle swelling, vomiting, rashes, recent infe ctions (sore throat), weight loss, hair loss, darkening skin; PMH previous jaundice, gallst ones, blood transfusions; DH see box above; FH liver disease, recent jaundice; SH alcohol, IVDU, tattoos, piercings, foreign travel, sexual activity. Obs temp, HR, BP, RR, O2 sats, G CS, blood glucose, urine output. Look for volume status b p380; acute liver failure drowsin ess, confusion, slurred speech, jaundice, fl apping tremor (asterixis), poor co-ordination, bruising, foetor hepaticus (sweet, fecal smelling breath), abdominal tenderness, hepatomeg aly, ascites; chronic liver disease cachexia, palmar erythema, clubbing, xanthelasma, spide r naevi, caput medusa, gynaecomastia, muscle wasting, splenomegaly, genital atrophy, track marks (IVDU), pneumonia/chronic lung disease, darkened skin. Investigations These are aimed at establishing the extent and possible cause of liver damage, and fi nding a possible cau se of any decompensa- tion, especially intercurrent infection urine MSU; blds FBC, clotting , iron, ferritin, U+E, LFT, hepatitis serology (A, B+C), EBV and CMV serology, caeruloplasm in (if <50yr), autoimmune screen (antimitochondrial, antinu- clear and anti-smooth muscle a ntibodies, b p593), bld cultures; urgent USS abdo looking for parenchymal mass(es), dilated ducts or portal vein thrombosis; urgent ascitic tap (b p550) and white cell count to check for spontaneous bacterial peritonitis (b p316). _OHFP.indb 313 _OHFP.indb 313 30/05/2014 16:18 30/05/2014 16:18 314 CHAPTER 9 Gastroenterology 3Acute liver failure (OHAM3 b p268) Acute encephalopathy, coagulopathy and jaundice without previous cirrhosis (Table 9.10). Table 9.10 Types of acute liver failure Liver failure <7d of disease onset Liver failure 1 \200\2234wk of disease onset Liver failu re 4 \200\22312wk of disease onset Liver failure 12 \200\22326wk of disease onset Late-onse t hepatic failure Hyperacute fulminant hepatic failure Acute fulminant hepatic failure Subacute fulminant hep atic failure Symptoms bruising/bleeding, drowsy confusion, abdo pain. Signs drowsiness, confusion, slurred speech, jaundice, fl apping tremor (asterixis), poor c o-ordination, bruising, hepatomegaly, ascites. Investigations initiate liver screen as deta iled (b p313) blds iPT/APTT, iiALT, iALP, ibilirubin, iammonia, iWCC, dglucose, dMg2+, dPO4 3 \200\223; ABG respiratory alkalosis, metabolic acidosis (poor prognosis); USS masses, ec hogenicity, portal vein fl ow. Treatment discuss with a senior early, often needs ICU/HDU with inva- sive monitoring, and may need transfer to a specialist liver center, where may be considered for transplantation . Monitor blood glucose every 2h; insert a catheter and monitor fl uid balance. \200 iPT give one-off dose of vitamin K 10mg IV: always discuss with a senior; PT prolongation is used to monitor disease progress; FFP may be indicated if the patient is bleeding or needs an invasive proc edure Stop aspirin, NSAIDs and hepatotoxic drugs (b p313); check all drugs in BNF Antibiotic prophylaxis in all patients (eg cefotaxime) antifungals \200 Daily bloods ( FBC, U+E, LFT, PT1) \200 Lactulose 10 \200\22320ml/8h PO in all patients (helps remove am monia) \200 Close monitoring of cardiovascular status and blood glucose; if need IV fl uids, avoid Na+ if chronic liver disease/ascites. Complications renal failure (hepatorenal syndrome), respiratory failure (ARDS), cerebral oe dema, bleeding, sepsis, dglucose, iNa+, dK+. Vascular liver disease Diagnosed by Doppler USS; these diseases can cause hepatic jaundice or acute liver failure, often treated by anticoagulation or endovascular methods. \200 Bu dd \200\223Chiari hepatic vein obstruction \200 Portal vein obstruction (pain and derange d LFTs; jaundice only if other causes of liver disease coexist) Liver ischaemia due to hypotension and/or hepatic artery stenosis. Typically causes massive ALT rise. 1 Strictly, the INR is specifi c for warfarin therapy; the pattern abnormal clotting in liv er disease is diff erent and more reliably reported as PT and APTT prolongation. OHFP.indb 314 OHFP.indb 314 30/05/2014 16:18 30/05/2014 16:18 315 LIVER FAILURE Glandular fever (infectious mononucleosis, Epstein \200\223Barr virus, EBV) Symptoms usuall y young (10 \200\22330yr), sore throat >1wk, fever, lethargy, malaise, rash, lumps in the n eck, anorexia. Signs red tonsils white exudate, tender lymphadenopathy, splenomegaly, ras h (especially with amoxicillin/ampicillin), palatal petechiae, jaundice. Investigations bld s ilymphocytes (atypical on fi lm), iALT, +ve Monospot/Paul Bunnell, +ve IgM for EBV. Manag ement rest, rehydration, analgesia, gargle with warm saline/ aspirin, avoid amoxicillin/amp icillin, avoid alcohol, consider short course of oral steroids if very severe (eg hepatic e ncephalopathy). Complications hepatitis, liver failure, thrombocytopenia, splenic rupture, haemolysis, encephalitis. Acute viral hepatitis (OHCM9 b p406) Causes hepatitis A,B,C and E , cytomegalovirus (CMV) and EBV. Symptoms jaundice, rash, diarrhea, abdo pain, fl u-like sy mptoms (eg fever, malaise, anorexia, fatigue, nausea, vomiting, arthralgia, sore throat). S igns may have no signs, itemp, urticarial rash, jaundice, hepatomegaly, splenomegaly, lymph adenopathy. Investigations blds iWCC, ibilirubin, iALT iPT, +ve hepatitis serology (Table 9.11). Management avoid alcohol, supportive treatment, monitor for progression to acute li ver failure (b p314) which may need interferon-A. Complications natural history varies wide ly depending upon virus and host; risks include acute liver failure or chronic disease. Chr onic viral hepatitis (OHCM9 b p406) Hepatitis >6mth, caused by hepatitis B ( D) and C. Sym ptoms and signs usually asymptomatic, signs of chronic liver disease. Investigations blds d eranged LFT iPT; abnormal viral serology (Table 9.11); USS liver may be suggestive of cir rhosis. Treatment avoid alcohol, consider referral to a hepatologist for specifi c antivira l treatment (eg interferon-A or ribavirin).1 Complications cirrhosis (20%), hepatocellular carcinoma (esp HBV). Table 9.11 Serology in hepatitis B Surface antigen (HBsAg) Active virus replication \200\223 acute or chronic disease Anti-co re (Anti-HBc) IgM Acute infection Anti-core (Anti-HBc) IgG Chronic infection (or previous i nfection if HBsAg \200\223ve) \200\230e \200\231 antigen (HBeAg) Anti-e (Anti-HBe) High infectivity Low infectivity In chronic hepatitis B infection, HBeAg negativity is associated with immune control of the virus and low/undetectable viral DNA. Beware, however, the subset of patients in whom the virus develops a precore mutation leading to absent production of HBeAg, despite loss of im mune control and rising viral DNA titres. These patients are at high risk for disease compl ications. 1 See (cid:27)www.bsg.org.uk/clinical-guidelines/liver/index.html for treatment guidance. _OHFP.indb 315 _OHFP.indb 315 30/05/2014 16:18 30/05/2014 16:18 316 CHAPTER 9 Gastroenterology Decompensated chronic liver failure (OHCM9 b p260) Cirrhosis is the fi nal common histologi cal pathway for a variety of liver diseases; problems relate to synthetic function (coagulo pathy, ascites 2 \232 to hypoalbuminaemia), decreased detoxifi cation (encephalopathy), or portal hypertension (variceal bleeding). Symptoms and signs as for acute liver failure (b p 314) but look for stigmata of chronic liver disease: spider angioma, palmar erythema, gynae comastia. Investigations measure severity: LFTs, U+E and clotting profi le; establish under lying cause: hepatitis serology, immunoglobulins, liver autoantibodies, ferritin, A1-antitr ypsin, ceruloplasmin, USS, liver biopsy; identify precipitant of decompensation: FBC, bld c ultures, ascitic tap, OGD. Treatment requires hepatology input and transplant assessment; d eal with upper GI bleeding (b p299), treat sepsis, support alcohol cessa- tion, lactulose ( to reduce ammonia levels). Ascites low-salt diet, daily weights, spironolactone 100mg/24h P O increasing dose every 48h to 400mg/24h furosemide; ascitic tap for diagnosis (b p550) a nd to exclude spontaneous bacterial peritonitis; may need long-term antibiotics, therapeuti c paracentesis or TIPS if recurrent. Complications high mortality, portal hypertension, ble eding varices, encephalopathy, hepatocellular carcinoma. Spontaneous bacterial peritonitis Symptoms abdominal pain in the presence of ascites, assoc iated with fever. Signs fever, iHR dBP, abdo tenderness peritonitis. Investigations bld s iWCC, iCRP; ascitic tap >250 white cells/mm3 or identifi cation of organisms (b p550). Tr eatment prompt IV antibiotics: (eg Tazocin 4.5g/8h IV). Autoimmune liver disease (OHCM9 b p266) Causes primary biliary cirrhosis (b p319), primary sclerosing cholangitis (b p319), autoimmune hepatitis (type I and II \200\223 see below); primary biliary cirrhosis and typ e I autoimmune hepatitis may overlap. Symptoms often asymptomatic, may have fever, malaise, rash, joint pain or symptoms of chronic liver disease. Signs of chronic liver disease. Inv estigations blds deranged LFT iPT, +ve autoantibodies (Table 9.12); USS and liver biopsy. Treatment autoimmune hepatitis prednisolone 30mg/24h PO initially then azathioprine; other diseases see b p319. Complications acute liver failure, cirrhosis, hepatocellular carcinom a. Table 9.12 Autoantibodies in autoimmune liver disease Primary biliary cirrhosis (780% 5) Anti-mitochondrial (AMA) present in 95% and 98% specifi c Anti-smooth muscle (SMA), antinuc lear (ANA), p-ANCA Primary sclerosing cholangitis (770% 5, 780% IBD) Autoimmune hepatitis type I (80% 5) Anti- smooth muscle (SMA), antinuclear (ANA) Anti-liver/kidney microsomal type 1 (LKM1) Autoimmune hepatitis type II (mainly children; 90% 5) OHFP.indb 316 OHFP.indb 316 30/05/2014 16:18 30/05/2014 16:18 317 LIVER FAILURE Haemochromatosis (OHCM9 b p262) Autosomal-recessive disease causing excess iron accumulatio n. Symptoms fatigue, lethargy, arthralgia, hyperpigmentation, DM. Signs hepatomegaly, signs of chronic liver disease, cardiac failure or con- duction defects, hypogonadism impotenc e, tanned skin. Investigations blds itransferrin saturation (>60% in 4 and >50% in 5 highly specifi c, but false negatives esp. in younger 5),iALT, iglucose, genetic testing (2 commo n mutations account for 70% of Caucasian patients); ECG cardiomyopathy or conduction delays ; liver biopsy (diagnosis, severity). Treatment venesection (1 unit/wk) until ferritin norm alizes then every 3 \200\2236mth; transferrin saturation or genetic screening of relatives. A1-antitrypsin de \201 ciency (OHCM9 b p264) Genetic disease with complex inheritance cau sing liver and lung damage. Symptoms breathlessness, liver failure, family history. Signs e mphysema, signs of chronic liver disease. Investigations blds dA1-antitrypsin levels, genet ic testing; liver biopsy. Treatment stop smoking, may need liver transplant, COPD treatment . Wilson \200\231s disease (OHCM9 b p269) Autosomal-recessive disease; copper accumulates i n the liver and CNS. Symptoms tremor, slurred speech, abnormal movements, clumsiness, depre ssion, personality change, psychosis, liver failure, family history. Signs Kaiser \200\223F leischer rings in eyes, signs of liver failure. Investigations blds dcaeruloplasmin, dtotal serum copper, iserum free copper, genetic testing; urine i24h copper excretion (especially if a dose of penicillamine is given); copper on liver biopsy. Treatment lifelong penicilla mine, may need liver transplant, screen relatives. Weil \200\231s disease (leptospirosis) B acterial infection typically transmitted via exposure of skin cuts or mucous membranes to w ater contaminated with rat urine. Symptoms recent contact with dirty water, high fever, mal aise, anorexia, fatigue, nausea, vomiting, arthralgia, pharyngitis, conjunctival oedema, ne ck stiff ness, photophobia, jaundice, bleeding and kidney failure. Signs acute liver failur e, meningism, bruising, tender RUQ, myocarditis. Investigations urine dipstick haematuria, culture; blds dHb (haemolytic), iurea, icreatinine, ibilirubin, iALT, serology. Treatment d oxycycline 100mg/12h PO or benzylpenicillin 600mg/6h IV and supportive care of renal/liver failure. pp Predicting outcomes in chronic liver disease is of considerable importance, not least in pr ioritizing use of organs for transplantation. The \200\230Child \200\231 scoring system or iginated in 1964 from attempts by Child and Turcotte to assess operative risks for cirrhoti c patients undergoing porto-systemic shunt surgery. Later modifi cations to include albumin and INR led to the \200\230Child \200\223Turcotte \200\223Pugh \200\231 score which is st ill widely used. With the advent of liver transplantation more precise stratifi cation of p atients with advanced disease was needed: For the NHS transplantation program, the UKELD (U K end-stage liver disease) score is calculated from serum Na+, creatinine, bilirubin and IN R. The original description of the UKELD score (Neuberger, J. et al., Gut 2008 57:252) is a vailable online at (cid:27)gut.bmj.com/content/57/2/252.abstract (subscription required, bu t many NHS trusts provide access through ATHENS). Online calculators for the Child score ar e widely available (eg (cid:27)www.mdcalc. com). Information on the NHS transplantation pro gram, including liver transplants and a UKELD calculator is available at (cid:27)www.organd onation.nhs.uk _OHFP.indb 317 _OHFP.indb 317 30/05/2014 16:18 30/05/2014 16:18 318 CHAPTER 9 Gastroenterology Jaundice Worrying features iHR, dBP, drowsiness, dGCS, bleeding, slurred speech, poor coordination, tremor/fl ap, renal failure, weight loss. Think about \200 Pre-hepatic haemolysis, malaria. \200 Hepatic paracetamol overdose, vi ral hepatitis, alcohol, chronic liver disease, Gilbert \200\231s syndrome, pregnancy, medications (b p319), toxins (eg poisonous fungi), vascular disease (eg ischaemia, Budd \200\223Chiari), sepsis. \200 Cholestatic ch oledocholithiasis, ascending cholangitis, pancreatic cancer, cholangiocarcinoma, primary bi liary cirrhosis, p sclerosing cholangitis. Ask about tiredness, jaundice (+onset), abdo pai n, itching, dark urine, pale stools, drowsiness, confusion, bruising, bleeding (skin, nose, bowel, urine), bloating, vomiting, rashes, recent infections (sore throat), weight loss, g eneralized aching, hair loss, darkening skin, joint pain; PMH previous jaundice, gallstones , breathing problems, blood transfusions; DH paracet- amol and medications (b p319); FH liv er disease, recent jaundice; SH alcohol, IVDU, tattoos, piercings, foreign travel, sexual a ctivity (?abroad). Obs temp, RR, HR, BP, urine output, O2 sats, glucose, GCS. Look for volu me status (b p380), bruising, evidence of bleeding, drowsi- ness, confusion: \200 Pre-hep atic splenomegaly, pale conjunctiva, breathlessness \200 Hepatic signs of acute or chroni c liver failure (b p313) \200 Cholestatic abdominal tenderness peritonism, Charcot \200 \231s triad (fever, jaundice and RUQ pain = cholangitis), palpable gallbladder, cachexia. I nitial investigations urine MSU, bilirubin, urobilinogen; blds FBC, reticulocytes and LDH ( both elevated in haemolysis), blood fi lm, clotting, U+E, LFT (total and conjugated bilirub in), amylase, lipase, paracetamol levels, hepatitis, EBV and CMV serology, bld cultures; ur gent USS abdo (?dilated bile ducts, cirrhosis, pancreatic mass, metastases). See Table 9.13 . Table 9.13 Laboratory investigation of jaundice Urine Urobilinogen iunconjugated Liver tests Other tests dHb, nMCV, dhaptoglobin, ireticulocytes May have positive hepatitis serology or iparacetamol levels Dilated ducts on USS Pre-hepatic jaundice Hepatic jaundice Cholestasis Bilirubin, dark urine bilirubin Urobilinogen imixed bilirubin, iALT/AST iconjugated bilirubin, iALP, iGGT iconjugated bilirubin, iALP, iGGT iWCC, iCRP, dilated biliary ducts Cholangitis Bilirubin, dark urine Causes of jaundice covered elsewhere b p394 b p313 Haemolysis Liver failure OHFP.indb 318 OHFP.indb 318 30/05/2014 16:18 30/05/2014 16:18 319 JAUNDICE Gilbert \200\231s syndrome Benign autosomal recessive disease causing mild, self-resolving unconju- gated hyperbilirubinaemia typically during acute illness. Choledocholithiasis Gall stone in common bile duct, causing obstructive jaundice. Risk factors 5, pregnancy, DM, obe sity, age. Symptoms often none, preceding biliary colic, dark urine, pale stool. Signs jaun dice, mild RUQ tenderness. Investigations blds iALP, ibilirubin; USS dilated bile ducts. Tr eatment maintain hydration, exclude pancreatitis and cholangitis, prophy- lactic antibiotic s (eg co-amoxiclav 1.2g/8h IV); ERCP permits diagnosis and stone removal; cholecystectomy u sually deferred until jaundice resolved. Complications pancreatitis, cholangitis, hepatitis , clotting defects. Cholangitis Infection of the bile duct with Charcot \200\231s triad: fe ver, jaundice, RUQ pain. Symptoms unwell, abdo pain, rigors, jaundice. Signs itemp, iHR d BP, RUQ tenderness (Murphy \200\231s +ve). Investigations blds iWCC, iCRP, ibilirubin; USS ?duct dilatation, stones. Treatment eg co-amoxiclav 1.2g/8h IV; may need an urgent ERCP if gall- stones are in the common bile duct. Primary biliary cirrhosis (OHCM9 b p266) Chronic, progressive autoimmune destruction of interlobular bile ducts. Symptoms and signs fatigue, pruritus, cholestatic jaundice, cirrhosis. Investigations blds iALP, iGGT ibilirubin, iI gM, anti-mitochondrial antibodies (b p316); USS liver biopsy for staging. Treatment ursod eoxycholic acid (helps symptoms and delays progression); colestyramine 4 \200\2238g/24h PO for itching; monitor for signs of decompensation and screen for osteoporosis (DEXA); in adv anced disease immunosuppres- sion (eg methotrexate, steroids); replace fat-soluble vitamins (A, D, E, K); refer for liver transplant assessment. Primary sclerosing cholangitis (OHCM9 b p267) Infl ammation and fi brosis of intra- and extrahepatic bile ducts. Symptoms and si gns chronic biliary obstruction leading to cirrhosis; IBD present in 780%, of which 790% UC , but course of IBD not related to PSC. Investigations blds iALP, ibilirubin, iimmunoglob ulin levels, anti-smooth muscle antibodies (SMA), antinuclear antibodies (ANA), p-ANCA, HLA -A1, B8 or DR3; ERCP multiple strictures; fi brosis on liver biopsy. Treatment trials of im munosuppressive agents have proven disappointing; ursodeoxycholic acid can help symptoms; s creen for osteoporosis (DEXA) and monitor for cholangiocarcinoma (71% per annum); transplan - tation key, but disease recurs in 15% post transplant. Cholangiocarcinoma (OHCM9 b p270) Adenocarcinoma (90%) or squamous cell carcinoma of intra- and extra- hepatic biliary epithe lium; strong relationship with IBD and PSC. Symptoms and signs jaundice, pruritus, weight l oss, dull RUQ ache. Courvoisier \200\231s law an enlarged gallbladder in the presence of ja undice is not caused by gallstones (suggests pancreatic or biliary cancer). Investigations blds iALP, ibilirubin, CA19.9; USS, MRCP, ERCP 9 biopsy. Treatment surgery (10 \200\22340%) ; else palliate: chemotherapy, ERCP + stenting. _OHFP.indb 319 _OHFP.indb 319 30/05/2014 16:18 30/05/2014 16:18 This page intentionally left blank Chapter 10 Endocrinology 321 Hypoglycaemia emergency 322 Hypoglycaemia 323 Hyperglycaemia emergency 324 Hyperglycaemia 3 25 Sliding scales 327 Diabetes mellitus 328 Pituitary axis 331 Adrenal disease 332 Thyroid disease 334 _OHFP.indb 321 _OHFP.indb 321 30/05/2014 16:18 30/05/2014 16:18 322 CHAPTER 10 Endocrinology Hypoglycaemia emergency Check airway is patent; consider maneuvers/adjuncts If no respiratory eff ort \200\223 CAL L ARREST TEAM Airway Breathing Circulation If no palpable pulse \200\223 CALL ARREST TEAM Disability If GCS \211 8 \200\223 CALL anesthetist 3Call for senior help early if patient deteriorating. \200 Blood glucose is normally >3.5 mmol/l \200 Poorly controlled diabetics can have symptoms of hypoglycaemia with a glucose >3.5mmol/l. Coma or low GCS with low glucose \200 Protect airway \200 15l/min O2 if SOB or sats <94 % \200 Establish venous access unless already present \200 Give IV glucose STAT (100ml of 20% or 200ml of 10%) \200 For large insulin overdoses give 1mg glucagon SC/IM/IV \200 Begin to follow emergency protocol on b p338 (low GCS) \200 If hypoglycaemia is respons ible, GCS should return to 15 in <10min \200 Start 1l 10% glucose/4 \200\2238h IV, adjust rate to keep glucose >5mmol/l Monitor \201 nger-prick glucose every 30min \200\2231h until patient stable \200 Attemp t to determine the cause of the hypoglycaemia \200 Call for senior help \200 Reassess, starting with A, B, C; if no improvement see b p338. GCS 15/15 with low glucose \200 Give at least 120ml Lucozade or a single dose of glucose gel (GlucoGel ) orally (this will o nly last up to an hour, so give a sandwich too) Monitor \201 nger-prick glucose 1 \200\2232h until stable, aim for >5mmol/l \200 For pe rsistent hypoglycaemia give 1l 10% glucose/6 \200\2238h IV \200 Attempt to determine the cause of the hypoglycaemia. Life-threatening causes Insulin overdose \200 Oral hypoglycaemia overdose \200 Sepsis Alcohol excess \200 Acute liver failure OHFP.indb 322 OHFP.indb 322 30/05/2014 16:18 30/05/2014 16:18 323 HYPOGLYCAEMIA yp g y Hypoglycaemia Worrying features dGCS, recurrent episodes, loss of awareness,1 non-di abetic. Think about most likely excess insulin or oral hypoglycaemics in a dia- betic or accidental dose in non-diabetic, alcohol; other dumping syndrome (DM or post-gastric surgery), liver failure, adrenal failure (Addison \200\231s), pitu- itary insuffi ciency, sepsis, insulinom a, other neoplasia, malaria. Ask about sweating, hunger, exercise, recent food, previous hy pos and awareness,1 usual blood sugars, seizures, weight loss, tiredness, anxiety, palpitat ions; PMH DM, gastric surgery, liver or endocrine disease; DH insulin dose, oral hypoglycae mic dose, compliance; SH alcohol. Obs HR, BP, RR, temp, GCS, recent and current blood gluco se. Look for pale, sweating, tremor, slurred speech, focal neurology (can be severe, eg hem iplegia), dGCS, abdo scars (injection sites, lipodystrophy), pigmented scars, jaundice, spi der naevi, hepatomegaly. Investigations \201 nger-prick glucose \200\223 if the result i s unexpected ask for a repeat on a diff erent machine and send a blood sample in a fl uorid e oxalate (b p517) tube for a laboratory glucose result. If not known to be diabetic send s amples for FBC, U+E, LFT, glucose, insulin and C-peptide prior to correcting hypoglycaemia, but do not let this delay your treatment. Further investigations hypoglycaemia is very rar e in an otherwise healthy non-diabetic patient in the absence of alcohol. Consider other causes listed above. For suspected insulinoma, the investigation of choice is glucose, insu lin and C-peptide levels after a 72h observed fast. Gut hor- mones may also be requested. S ee OHCM9 b p206. Treatment follow treatment for \200\230Hypoglycaemia emergency \200\231 ( b p322). DM A single episode of mild hypoglycaemia should not prompt a change of medication . If the patient is having regular hypos then consider a dose reduction, especially if lack of awareness of hypoglycaemic episodes. Try to establish any diurnal pattern of hypos, the n reduce appropriate insulin dose by 20%; consult BNF to reduce the doses of oral hypoglyca emics. Ensure the patient is aware of the sick day rules (b p329). Alcohol hypoglycaemia fo llowing alcohol will not reoccur after correction in the absence of further alcohol consump tion. Once the patient \200\231s blood sugars are stable they can be discharged. Dumping sy ndrome fast passage of food into the small intestine (following gastric surgery or in sever e diabetic autonomic neuropathy) can cause fl uid shifts and rapid glucose absorption. Exce ssive insulin secretion results in rebound hypoglycaemia 1 \200\2233h after a meal. A diet low in glucose and high in fi bre will improve the symptoms. pp p Neoplasia if suspected, a rrange appropriate imaging and referral p g g g p b p332/331 b p480 b p314 Addison \200\231s/pituitary failure Sepsis Acute liver failure 1 Loss of early autonomic symptoms warning of mild hypoglycaemia (eg tremor, sweating) seen in those with longstanding DM and frequent hypoglycaemic episodes. _OHFP.indb 323 _OHFP.indb 323 30/05/2014 16:18 30/05/2014 16:18 324 CHAPTER 10 Endocrinology Hyperglycaemia emergency Check airway is patent; consider maneuvers/adjuncts If no respiratory eff ort \200\223 CAL L ARREST TEAM Airway Breathing Circulation If no palpable pulse \200\223 CALL ARREST TEAM Disability If GCS \211 12 \200\223 CALL anesthetist 3Call for senior help early if patient deteriorating. Diabetic ketoacidosis (DKA) \200\223 see b p326 \200 15l/min O2 if SOB or sats <94% \200 Call for senior help \200 Establ ish venous access, take bloods: \210\222 3, bld cultures \200 FBC, U+E, glucose, osmolal ity, HCO Check BP: if SBP<90mmHg, give 500ml 0.9% saline IV over 10 \200\22315min then recheck; if SBP<90, give further 500ml 0.9% saline IV over 10 \200\22315min and call I CU/critical care teams. \200 if SBP \211 90, give 1l 0.9% saline IV over 60min Check \201 nger-prick glucose and ketones (dipstick urine for ketones if capillary testing unavailable) Start a \201 xed rate insulin infusion of 0.1unit/kg/h IV (use 50 units human soluble insulin eg Actrapid in 50ml 0.9% saline) \200 Venous blood gas; if pH <7.1 call ICU/critical care team \200 Monitor glucose and ketones hourly, and venous H CO \210\222 3 and K+ at 60 min and 2hrly thereafter; remember K+ will fall unless replaced \200 Further managemen t, b p326; ECG, CXR, MSU to determine cause \200 Reassess, starting with A, B, C \200 R eassess, starting with A, B, C \200 Consider HDU admission in DKA for: Heart or kidney failure \200 GCS <12, Sats <92% \200 SBP <90 Young people, elderly, comorbidities or pregnant \210\222 \200 Ketones >6mmol/l, HCO 3 < 5mmol/l, pH <7.1 \200 K+ <3.5mmol/l, anion gap >16 b p585 Hyperosmolar non-ketotic state (HONK) \200\223 see b p326 \200 15l/min O2 if SOB or sats <94% \200 Call for senior help \200 Establish venous access, take bloods: FBC, U+E, glucose, osmolality, bld cultures Give 1l 0.9% saline IV over 30min \200 Check \201 nger-prick glucose \200 Start a sli ding scale if glucose still raised after 1h of fl uids, see b p326 \200 Monitor U+E and g lucose \200 Further management, b p326; ECG, CXR, MSU to determine cause \200 Reassess, starting with A, B, C \200 Life-threatening precipitants of DKA/HONK Sepsis \200 MI Trauma/surgery \200 Other acute illness OHFP.indb 324 OHFP.indb 324 30/05/2014 16:18 30/05/2014 16:18 325 HYPERGLYCAEMIA Hyperglycaemia Worrying features dGCS, ketonuria, acidosis, vomiting. Think about emergencies diabetic ketoacidosis (DKA, b p326), hyper- osmolar non-ketotic sta te (HONK, b p326); common after sugary food, steroids, non-compliance with diabetic treatme nt, infection or acute illness (in diabetics or severely unwell non-diabetics), new diagnos is of DM. Ask about \200\230osmotic symptoms \200\231 (thirst, polyuria, frequency, urgency), tiredn ess, weight loss, vomiting, rashes, breathlessness, cough, sputum, chest pain, abdo pain, d ysuria; PMH DM; DH insulin dose, oral hypogly- caemic dose, medication changes and complian ce, steroids; SH alcohol. Obs temp, RR, GCS, recent and current blood glucose, fl uid balance. Look for volume status (b p380), sweet-smelling breath (ketones): signs of infection: check skin thoroughly (incl uding perineum and feet) for abscesses or rashes, look in mouth for dental infection, chest for poor air entry or creps, abdominal tenderness. Investigations \201 nger-prick glucose ( ketones if available and suspect DKA) repeat if result unexpected; urine dipstick ketones, evi- dence of infection (b p590); blds send if patient is unwell, has per- sistent hyperglycaemia (over 48h) or has urinary ketones (type 1 DM), \210\222 request FBC, U+E, LFT, osmolality, pH/HCO 3 (venous), blood cultures; ABG unnecessary unless concerns regarding respiratory status (venous pH adequate for DKA); ECG/ CXR if treatment has been required. Treatment a single episode of hyperglycaemia in an otherwise well patient is unlikely to su ggest underlying pathology. DKA takes hours to days to develop whilst HONK takes days to we eks. Type 1 diabetes Check fi nger-prick glucose ( ketones if available) and urine. Glucose is usually high in DKA but may be transiently normal soon after a dose of insulin. Assess volu me status (b p380), check dipstick \210\222 for ketonuria and check a venous blood gas for pH/HCO 3 (normal venous pH or absence of urinary ketones excludes DKA). If hypergly- caemi a persistent try to establish any diurnal pattern and i appropriate insulin doses by 20% wi th close monitoring of blood glucose. Type 2 diabetes Check fi nger-prick glucose and urine. The glucose must be raised for a dia gnosis of HONK. If unwell follow the treatment plan for HONK initially. Otherwise monitor g lucose levels every 6h for 48h, increase oral/IV fl uid intake and reassess. DKA can occur in type 2 diabetics who require insulin but it is very unusual (even low levels of residual insulin production inhibit ketogenesis). For persistent hyper- glycaemia increase the dose of hypoglycaemic medication or consider starting/increasing insulin with frequent fi nger- prick glucose checks. Non-diabetic patients New diabetics often present with DKA/HONK; have a low threshold for s tarting treatment plans later in this section. Other triggers can include steroids, pregnan cy and stress, eg severe illness or surgery. _OHFP.indb 325 _OHFP.indb 325 30/05/2014 16:18 30/05/2014 16:18 326 CHAPTER 10 Endocrinology Diabetic ketoacidosis (DKA)1 (OHAM3 b p516) Insulin defi ciency resulting in hyperglycaemia and dehydration. Ketone body formation leads to acidosis and ketonuria. Typically seen fol lowing missed insulin treatments or infection in T1DM, or as a fi rst presentation of T1DM. \200 Diagnose based upon presence of hyperglycaemia ( \211 11mmol/l), acidosis (venous pH<7.3) and blood ketones \211 3mmol/l or ketonuria( \211 2+). Stabilize the patient as shown on b p324, then: Continue IV insulin infusion and fl uid rehydration (see box) \210\222 \200 Monitor veno us K+, pH and HCO 3 after 1h, 2h and then 2hrly using a venous sample on a gas analyzer for rapid testing Monitor venous glucose and ketones hourly aiming for blood ketones to fall by >0.5 mmol/l/h and glucose by >3mmol/l/h If patient uses long-acting insulin continue at normal dose/time \200 Continue insulin in fusion until ketones <0.3mmol/l and pH>7.3. At this point convert to regular SC insulin if eating and drinking normally, else use a slidin g scale (b p327). DKA \202 uids 0.9% saline is the most appropriate fl uid replacement. A guide in adults w ould be to prescribe 1l over 1h, 1l over 2h, 1l over 2h and 1l over 4h. If systolic BP <90m mHg on admission an initial 500 \200\2231000ml bolus must be carefully given under senior s upervision. Since excess fl uid replacement can lead to cerebral oedema, reassess frequentl y for signs of overload (b p380), and tailor to volume status and patient weight. Add 40mmo l/l KCl after the fi rst liter of fl uid if the plasma K+ is 3.5 \200\2235.5mmol/l. Omit ad di- tional KCl if K+ >5.5; if K+ <3.5 seek senior review. Adding a 10% glucose infusion at 125ml/h if glucose <14mmol/l but do not stop saline. Management tips in DKA/HONK These patients require close monitoring. If severely ill, cathe terise, consider admission to HDU or ICU and an arterial and/or central line. If obtunded o r persistent vomiting, keep NBM and pass NG tube. Dehydration and dGCS predispose to thromb oembolism: give pro- phylactic LMWH (b p406). Consider likely precipitants: poor compli- an ce/incorrect insulin dose, alcohol, infections (may be asymptomatic \200\223 check blood c ultures, MSU and CXR; low threshold for starting anti- biotics), MI (check an ECG), CVA, su rgery. Hyperosmolar non-ketotic state (HONK) (OHAM3 b p524) Severe, uncorrected hyperglycaemia lea ds to dehydration, but in the presence of residual insulin production in T2DM, ketoacidosis does not develop. Also referred to as hyperosmolar hyperglycaemic state (HHS). Diagnose ba sed upon raised plasma osmolality2 (typically >340 mOsmol/kg) with high glucose (typically >30mmol/l). \200 Stabilize the patient as shown on the treatment plan, b p324, then: \200 Continue IV fl uid replacement (eg at half the rate used in DKA) \200 Monitor U+E, glucose and osmolality every 2h. Be aware that hyperglycaemia will drive redistribution of water into the extracellular fl uid, lowering s erum Na+ concentrations ( \200\230spurious hyponatraemia \200\231) Convert to insulin/oral hypoglycaemics when glucose <12mmol/l. 1 Joint British Diabetes Soc ieties guidelines at (cid:27)www.diabetologists-abcd.org.uk/JBDS_DKA_ Management.pdf 2 Plasma osmolality may be estimated as 2x([Na+] + [K+])+ urea + glucose whilst awaiting a formal lab measurement. OHFP.indb 326 OHFP.indb 326 30/05/2014 16:18 30/05/2014 16:18 327 SLIDING SCALES Sliding scales These give strict monitoring and control of blood glucose levels. They are u sed in the treatment of HONK, for diabetic patients requiring insulin whose oral intake is signifi cantly disrupted (eg NBM, severe vomiting or serious illness), and in critical illn ess, where good gly- caemic control improves outcomes, eg post-MI or on ICU. You need to pr escribe both the insulin infusion and appropriate IV main- tenance fl uids on the infusions section of the drug card (Fig. 10.1). Use 0.9% saline or 5% glucose (with KCl as necessary ), according to the blood glucose (use 0.9% saline if the glucose is running >11mmol/l). Date Route Fluid Additives Vol Rate Signature 18.8.14 IV 0.9% saline 50units Actrapid 50ml Sliding Scale P Roluos 18.8.14 IV 5% glucose 20mmol KCl 1l 8h P Roluos Fig. 10.1 Prescribing insulin and fl uids for a sliding scale. Insulin Date Start time Blood glucose (mmol/l) <4 4 \200\2237 7.1 \200\22311 11.1 \200\22320 >20 Rate (ml/h) Actrapid Dose 1unit/ml 18.8.14 Route IV 13:45 Stop \200\223 call doctor 1 2 4 7 \200\223 call doctor Signature S Dixon Fig. 10.2 Example of sliding scale regimen (check local guidelines). If the patient remains hyperglycaemic despite the sliding scale (Fig. 10.2) then check the infusion pump and cann ula; if no problems found, pre- scribe a STAT bolus of short-acting insulin eg Actrapid 4 \200\2236 units SC. If control still poor, increase infusion rates by 1.5 \200\2232-fold, and check venous pH (T1DM) or osmolality (T2DM). If the capillary blood glucose is <4mmol/l check that there is 5% glucose running, increase the fl uid rate and/or glucose concentrat ion (up to 10%); recheck glucose in 30min. If persistently <4mmol/l stop the sliding scale, and restart the infusion at half the doses once blood glucose >6mmol/l. If glucose <2, see b p322. Stop a sliding scale once a patient is eating normally and able to resume normal d iabetes medication. Give normal dose of SC insulin 30mins before stopping the scale, unless rapid acting (eg Novorapid , Humalog ) in which case give at same time as stopping the s cale. Prescribing insulin Most hospitals have separate drug cards for prescribing insulin. Always specify the insulin formulation, and avoid using the abbreviation \200\230U \200\231 for units (since this can be misread as a number). See Fig. 10.3 for an example. Breakfast Insulin Novomix 30 Dose (units) Route Start 18 SC 18.8.14 Night Insulin Novomix 30 Dose (units) Route Start 10 SC 18.8.14 Fig. 10.3 Prescribing subcutaneous insulins. _OHFP.indb 327 _OHFP.indb 327 30/05/2014 16:18 30/05/2014 16:18 328 CHAPTER 10 Endocrinology Diabetes mellitus Fasting plasma glucose \211 7.0mmol/l, or \211 11.1mmol/l 2h after a 75 g oral glucose load (given in 300ml water as oral glucose tolerance test \200\223 OGTT).1 \200 Type 1 autoimmune pancreatic B cell destruction, resulting in dependence on exogenous insulin; typically presents in children or young adults Type 2 relative insulin hyposecretion or resistance to eff ects, requiring drugs to potenti ate insulin secretion or eff ects, or exogenous insulin; typically occurs in adults, especi ally if overweight \200 Impaired glucose tolerance (IGT) plasma glucose \211 7.8mmol/l a fter OGTT, but <11.1mmol/l; 20 \200\22350% progress to T2DM in 10yr Impaired fasting glucose (IFG) plasma glucose \211 6.1mmol/l after an overnight fast, but <7.0mmol/l; lower risk of developing T2DM \200 Gestational any degree of glucose intolerance fi rst detected during pregnancy (b p505); around 30% will progress to T2DM within 5yr. Type 1 DM (OHCM9 b p198) Symptoms tiredness, weight loss, thirst, polyuria, abdo pain, vomi ting. Signs sweet-smelling breath, shock, abdominal pain (all suggest DKA). \210\222 Investigations Glucose testing as above. Check venous HCO 3 and pH and urine (ket ones) to exclude DKA. If uncertainty about type of dia- betes, positive islet cell or gluta mic acid decarboxylase antibodies, or low C-peptide levels all suggest T1DM. Check HbA1C (s ee box). Treatment resuscitate and investigate for DKA; in the absence of DKA, a new diagnosis of T1 DM does not necessitate admission, but the patient should be started on a suitable insulin regimen by an appropriately experi- enced individual (eg endocrine registrar or diabetes nu rse specialist) with regular fi nger-prick glucose monitoring and prompt out-patient follow -up. For properties of some commonly used insulins, see b p203. Chronic management \200 \223 see b p330.