Endocrinology


Endocrinology


Matthew Sims


Outline





Initial Assessment








Initial Investigations



ent VBG: Assess for metabolic acidaemia (due to ketosis)


ent Capillary or urinary ketone measurement: Capillary is preferred if available. Capillary ketones are a measure of 3-hydroxybutyrate. Urinary ketones measurement includes 3-hydroxybutyrate and acetoacetone, but is less precise and subject to inter-reader variability


ent FBC, U&Es, chloride, bicarbonate, plasma glucose, CRP, and blood cultures: Looking for evidence of infection, renal failure, and to confirm the glucose level. In the context of a metabolic acidaemia, bicarbonate and chloride are useful to calculate the anion gap


ent Troponin: Indicated in patients with chest pain/high risk of ischaemic heart disease–not in this case


ent CXR: Part of a septic screen


ent Urine dipstick: Look for leucocytes and/or nitrites, which would be consistent with infection


ent Pregnancy test: If detected, current pregnancy would impact upon the investigation and management of this patient. Her abdominal pain could be related to a complication of pregnancy


ent Renal USS: To help confirm the diagnosis of pyelonephritis



‘VBG: pH 7.11, PCO23.8 kPa, HCO35.8 mmol/L, BE−21.2 mmol/L. Capillary ketones are 6 mmol/L. Hb 125 g/L, WCC 17×109/L, neutrophil 15.6×109/L, platelet 198×109/L. CRP 250 mg/L. Urea 12.3 mmol/L, creatinine 134 µmol/L, Na 146 mmol/L, K 5.8 mmol/L, Cl 99 mmol/L. Glucose 31 mmol/L. Anion gap is 47 mmol/L [(Na+K)−(Cl+HCO3)=(146+5.8)−(99+5.8)=47 mmol/L]. CXR is normal. Urine dipstick+1 nitrites,+1 leucocytes.’




Blood gases


ABGs are more painful than taking VBGs. Unless there is a specific reason to look at PO2, diagnosis and monitoring of the patient’s acid–base status can be done with VBGs. image



Initial Management [1]



ent IV fluids: First priority is to rehydrate. Maintain good fluid balance by measuring hourly urine volumes and consider a catheter; 0.9% sodium chloride is the rehydration fluid of choice, to replace not only water, but also correct sodium and chloride deficits


ent In DKA, typical water deficit is 100 mL/kg, therefore for a 70 kg person, about 7 L of IV fluid may be needed in the first 24 hours. This should be given faster initially (i.e. 2–3×1 L bags over 1–2 hours), with regular titration of the rate depending on patient response (RR, HR, BP, urine output)


ent Fixed rate IV insulin infusion: This is not the same as a variable sliding scale (in which the rate of an insulin infusion is titrated against the blood glucose). The role of soluble insulin in DKA is to bring down the serum glucose but, more importantly, to suppress ketone production. Insulin should not be stopped until acidaemia has resolved and there is no remaining evidence of ketones


ent Insulin (Actrapid® or similar) should be commenced at 0.1 units/kg/h (70 kg×0.1 is 7 units/h in this case).


ent Continue or commence long-acting insulin analogues. This is to avoid rebound hyperglycaemia after discontinuation of IV insulin infusion. A typical starting dose for a normal weight person is 6 units of insulin glargine (Lantus®), although this can be altered depending on size (discuss with diabetes team)


ent Potassium replacement: Plasma potassium is often high on admission, but falls rapidly as IV insulin and fluid replacement are commenced. For this reason, it is important to monitor potassium regularly, and add potassium to ongoing maintenance fluids after initial resuscitation


ent Thromboprophylaxis: Sick medical patients are at risk of venous thromboembolism


ent Continue treatment of trigger: Regular co-amoxiclav should be given to treat the pyelonephritis (gentamicin here is given as a one off dose to broaden initial antibiotic cover). Give further paracetamol if temperature persists, or for any pain.





Definitive Management [1]


Ongoing management of this patient should involve the inpatient specialist diabetes team, senior medical doctors, and HDU or ITU staff depending on the clinical condition. The aim should be to resolve the ketonaemia and acidosis within 24 hours.



ent Ongoing IV fluids: If the patient has clinically responded to initial fast fluids (i.e. good urine output, falling HR, increasing BP), then the remaining fluid deficit can be replaced more slowly, e.g. 0.9% sodium chloride every 4 hours, based on regular clinical assessment, including a review of fluid balance, checking for clinical evidence of overload (i.e. increasing RR, wet crepitations in chest, and peripheral oedema), and GCS


ent Ketone monitoring and insulin infusion: Blood ketones should be measured hourly. The target is a fall of≥0.5 mmol/L/h. If measurement of blood ketones is not available, then rate of glucose fall and bicarbonate increase can be used as proxies (see below). If the ketone target is not met, then increase the insulin infusion at 1 unit/h until this is achieved. The insulin infusion can be stopped when the ketones are less than 0.3 mmol/L and the venous pH>7.3


ent Glucose monitoring and 10% glucose solution: Blood glucose should be measured hourly. A reduction of 3 mmol/L/h or greater is the target. If the glucose falls below 14 mmol/L while the insulin infusion is still required, start 10% glucose at 125 mL/h. This is in addition to, not a replacement for, the 0.9% sodium chloride infusion, as the latter is more effective for replacement of circulatory volume


ent VBG monitoring: This is for the measurement of pH, bicarbonate and K+. Repeat at one hour after initial assessment then every 2 hours for the first 6 hours. Frequency of measurement thereafter depends on the progress of the patient. The target increase in bicarbonate is>3 mmol/L/h


ent With the introduction of insulin and IV rehydration, the potassium will start to fall. If K+ is between 3.5 and 5.5 mmol/L, replace 40 mmol of potassium chloride with every 1 L of fluid given (but do not give more than 10 mmol/h of potassium). If<3.5 mmol/L, then more concentrated potassium solutions are likely to be needed: this may well require HDU


ent Follow-on care: Once ketonaemia and acidosis have resolved, the patient should be encouraged to eat and drink. A subcutaneous insulin regimen, often basal—bolus, will be needed for newly diagnosed patients. Known diabetic patients should be restarted on their SC insulin regimen, although this may need to be adjusted. The inpatient diabetes team should be involved, including patient (re-)education.





Initial Assessment








Initial Investigations



ent VBG: For confirmatory blood glucose, rapid Na result, and to assess acid–base status. Acidaemia could occur secondary to ketosis, or sepsis (raised lactate)


ent Bloods: FBC, U&Es, LFTs, CRP, glucose, blood cultures. Electrolytes can be deranged due to HHS and with subsequent fluid infusions. If available, (lab measured) osmolality should be requested. If this is not available then calculate this using the formula 2×Na++glucose+urea (estimated osmolality)


ent Capillary ketones: If available, otherwise look at urine ketones. This is important for determining whether insulin should be started earlier, and in determining whether this is DKA rather than HHS in situations where there is diagnostic doubt. If ketones are raised, they should be monitored


ent Urine dipstick: For markers of infection and for ketones


ent CXR: Look for consolidation


ent ECG: Look for evidence of cardiovascular precipitants of HHS including myocardial infarction


‘Bloods show Hb 134 g/L, WCC 16.7×109/L, platelets 198×109/L, urea 22 mmol/L, creatinine 170 μmol/L, K 3.7 mmol/L, Na 159 mmol/L. LFTs are normal. CRP is 123 mg/L. Glucose is 39 mmol/L. You calculate osmolality as 379 mosmol/kg (range 278–305). Capillary ketones are 0.3 mmol/L. Venous blood gas shows a metabolic acidosis with partial respiratory compensation. CXR shows consolidation at the right base. The ECG shows sinus tachycardia rate 116 bpm with no ST segment or T wave abnormalities.’




Initial Management [2]



IV fluids



ent IV fluids are used for the normalization of plasma osmolality, sodium, and glucose and to restore the circulating volume by replacing the considerable water and electrolyte deficit


ent In HHS, the plasma osmolality is significantly raised. High glucose is the significant contributor to this raised osmolality, but also plasma sodium and urea concentration are usually raised as well, further increasing the osmolality


ent There is a total body deficit of electrolytes (principally sodium, potassium, chloride), due to their renal loss secondary to an osmotic diuresis driven by glycosuria


ent The key to treating HHS is to avoid too rapid correction of osmolality, as this can be associated with seizures, cerebral oedema, and central pontine myelinolysis


ent Methods of avoiding rapid changes in osmolality include regular monitoring of clinical state, U&Es and plasma osmolality (see Definitive management). Furthermore, the rate of fluid administration needs to be carefully titrated and the fluid used should not be too hypotonic relative to the patient’s plasma. Therefore, 0.9% sodium chloride is the fluid of choice. In healthy patients, this is isotonic. In HHS patients, this is hypotonic. Therefore, 0.45% sodium chloride is too hypotonic and if used initially risks precipitating rapid osmotic shifts; 0.45% sodium chloride can be considered at a later stage in refractory cases when a more rapid osmotic shift is needed (see Definitive management)


ent In HHS, the extent of dehydration is typically more profound than in DKA, requiring up to 200 ml/kg of fluid replacement over 2 or more days.


ent Hourly urine volumes should be measured, therefore, consider a catheter particularly if the patient is immobile, confused, and/or incontinent.



ent Given Mrs Jones’s reduced GCS, she should be catheterized and started on a fluid balance chart


ent Insulin is not initially required: In the majority of cases, the plasma glucose should begin to correct with 0.9% sodium chloride alone. Remember there is no absolute insulin deficit. Indications for starting insulin immediately are blood ketones>1 or urine ketones>2, otherwise this should be initially postponed.


ent Replace potassium: This is required even if the potassium is within normal limits. Avoid giving potassium supplementation to those with K>5.5 mmol/L


ent Prescribe VTE prophylaxis: Patients with HHS are at high risk of VTE and should be prescribed LMWH. Mrs Jones’s Cockcroft–Gault creatinine clearance is 40.4 mL/min [(140–69)×93×1.04/170=40.4]. Anti-factor Xa level monitoring is only required in patients with an estimated GFR<20 mL/min, therefore, this may be required should her renal function worsen


ent Treat precipitant: In this case, this is likely to be a lower respiratory tract infection. She would qualify as severe community-acquired pneumonia (CURB 65 score=3 as over 65, confused, with a raised urea) and, therefore, add in clarithromycin 500 mg orally BD. Continue standard dose co-amoxiclav (it does not need to be renally adjusted until estimated GFR<30 mL/min). Paracetamol can be continued for pyrexia and pain control.





Definitive Management [2]



ent Ongoing management of this patient should involve the inpatient specialist diabetes team, senior medical doctors, and HDU or ITU staff depending on the severity of the clinical condition


ent Frequent monitoring of clinical hydration status, GCS and fluid balance every 1–2 hours, particularly looking for overload (i.e. SOB, wet crackles in the chest, peripheral oedema) and cerebral oedema (suggested by reduced GCS)


ent Measure blood glucose, Na, K, and calculate osmolality every hour for the first 6 hours, then, if biochemistry is normalizing, 2-hourly for 6 hours


ent Aim to gradually drop osmolality by 3–8 mosmol/kg/h and achieve a positive fluid balance of 2–3 L at 6 hours, and 3–6 L at 12 hours. Guidelines also suggest reducing plasma sodium by no more than 10 mmol/L/day. Note that full biochemical normalization is unlikely to be achieved within 24 hours


ent Insulin as a fixed rate intravenous insulin infusion at 0.05 units/kg/h, can be started once the blood glucose is falling at less than 5 mmol/L/h with adequate fluid balance. Adjust at 1 unit/h to achieve a target glucose between 10 and 15 mmol/L in the presence of adequate positive fluid balance


ent IV fluids against fluid balance: Increase the rate of IV fluids if target for positive balance is not met. If the osmolality is no longer declining despite adeqate fluid replacement with 0.9% sodium chloride, AND an adequate rate of fall of plasma glucose is not being achieved, then 0.45% sodium chloride should be used instead of 0.9% sodium chloride


ent Glucose replacement: If blood glucose falls below 14 mmol/L prescribe additional 10% glucose at 125 mL/h


ent Continue to treat and monitor for resolution of precipitant: In this case, the lobar pneumonia


ent Protect and monitor feet: There is a high risk of pressure ulceration. Apply heel protectors if patient is at high risk, e.g. obtunded with known peripheral neuropathy


ent Follow-on care: Once the patient is biochemically normal, eating and drinking, the insulin infusion can be discontinued (if started) and regular oral hypoglycaemics and/or SC insulin started. This should be in liaison with the diabetes team.




Station 6.3: Hypoglycaemia


You’re the junior doctor on shift in A&E resus with your registrar. A 16-year-old girl, Yasmin Grey, presents unconscious brought in by ambulance. Her accompanying friends tell you that they were at a party and 15 minutes before they found her she was ‘pretty drunk’ but seemed otherwise fine. An electronic discharge summary from 6 months ago states a new diagnosis of Type 1 diabetes.







image


Figure 6.7




Initial Assessment








Initial Investigations






This case is a good example of why a rigid approach to ABCD can occasionally lead to a loss of perspective and priority. This girl has a normal blood pressure (120/80) and urea. The tachycardic is due to her blood sugar of 1.3 mmol/L. She is young and will not die of dehydration but could be permanently damaged in minutes if she does not get any glucose. Therefore the IV glucose (under Disability) should be given before the fluid challenge (under Circulation). image



‘Initial bloods confirm hypoglycaemia with a blood sugar of 1.3 mmol/L. There is an associated CRP rise of 10 mmol/L, with a lactate of 3 mmol/L. Blood gas shows a metabolic acidosis. Breathalyser shows low levels of alcohol in the bloodstream, urine toxicology is negative, and paracetamol/salicylate levels are undetectable.’





Definitive Management



ent Regular ABCDE assessment, including capillary blood glucose needs to be continued, as there is a risk she’ll become hypoglycaemic again, particularly if she had injected a long-acting insulin


ent Replenish glycogen stores: The patient needs to eat a meal containing carbohydrate, e.g. two slices of toast


ent Complete history is now needed to determine the type of insulin injected, the dose injected and timing. Also check if any recreational drugs were taken


ent Counselling before discharge about compliance with diabetic medications, the importance of adjusting insulin when meal size varies, and trying to avoid binge-drinking


ent In cases of hypoglycaemia with no obvious precipitant, blood samples for insulin and c-peptide should be taken. If c-peptide levels are high this suggests increased endogenous insulin production, i.e. an insulinoma.


Nov 18, 2017 | Posted by in PHARMACY | Comments Off on Endocrinology
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