1000-2000 5 ьшò

Fruity odor of ketotic breath (acetone smell)

Decreased reflexes

Abdominal tenderness, decreased bowel sounds

Dry mucous membranes, poor skin turgor, dehydration

Altered mental status

Coma

DIFFERENTIALDIAGNOSIS

Hyperosmolar hyperglycemic crisis

Alcoholic ketoacidosis

Starvation ketosis

Toxic ingestions (e.g., salicylates, methanol)

Lactic acidosis

Uremia/chronic renal failure

Sepsis

Acute pancreatitis

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

ALERT

Diagnostic criteria (1)[C]:

–Hyperglycemia (glucose usually 250 to 800 mg/dL) as rapidly assessed on fingerstick glucose testing, and confirmed on serum chemistry

–Low HCO3 (usually ≤18 mEq/L)

–Metabolic acidosis on arterial blood gases (ABGs) (pH <7.3)

–Anion gap = serum sodium − (serum chloride + bicarbonate); >10 mmol

Other important labs:

–Serum ketosis: Check β-hydroxybutyrate (β-HB) instead of ketones to evaluate ketosis (2)[B]. β-HB is the predominant ketone produced and is preferred over serum ketones. β-HB >3 mg/dL is abnormal and should be decreased to <1.5 mg/dLwithin 12 to 24 hours (3)[B].

–Urine ketosis (urinalysis [UA]) may only identify acetoacetate and not β- HB.

–Increased creatinine and BUN: Markedly increased serum ketones may cross-react and cause a falsely high serum creatinine.

–Pseudohyponatremia: Hyperglycemia or hypertriglyceridemia may cause an artificially low sodium concentration. The measured sodium is

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suppressed by 1.6 mg/dL for every 100 mg/dL of glucose >100 mg/dL.

–Decreased calculated total body K+: Severe acidosis gives an artificially high K+ level.

–Increased serum osmolality (mOsm/kg) = [2 × serum Na (mEq/L) + glucose (mg/dL)/18 + BUN (mg/dL)/2.8]; if calculated osmolality <320 mOsm/kg, consider etiologies other than diabetic ketoacidosis (DKA).

–Elevated base deficit

–Hb A1c (glycosylated hemoglobin) helps assess long-term history of diabetic control.

–Glycosuria

–Hyperamylasemia, hyperlipasemia

–Hypertriglyceridemia/hypercholesterolemia

CBC, electrolytes, BUN, creatinine

Serum β-HB or ketones

ABG; venous blood gases (VBGs) may also be used (VBG pH correlates with 0.03 lower than ABG pH).

Urine and blood cultures if concern for infection

Troponin if concern for cardiac ischemia Other Tests

–ECG

Frequently shows sinus tachycardia (nonspecific)

Changes consistent with electrolyte abnormalities

Ischemia/MI as a precipitating factor

–Chest x-ray to rule out possible infectious etiology

–Consider lumbar puncture if concern for meningitis.

–Head CT scan if suspected CVAor cerebral edema

Diagnostic Procedures/Other

Only if surgical disease is the underlying precipitant (e.g., appendicitis, cholecystitis)

TREATMENT

Oxygen and airway management, as needed

Establish IV access.

Cardiac monitoring

Start isotonic crystalloid solution (e.g., 0.9% saline, or lactated ringers bolus).

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GENERALMEASURES

All, but mild cases require inpatient management.

Severe DKArequires an ICU setting.

Goals

–Fluid resuscitation

–Insulin therapy to normalize serum glucose

–Resolution of anion gap acidosis and ketosis

–Correction of electrolytes

Identify and treat the precipitating cause (e.g., insulin noncompliance, infection, MI)

Laboratory testing during management:

–Serum glucose q1–2h until stable

–Electrolytes, phosphorus, and venous pH q2–6h

MEDICATION

First Line

Insulin (1)[C]

–Optional initial bolus 0.1 U/kg IV and then continuous infusion at 0.1 U/kg/hr (do not use initial insulin bolus in children)

–If without bolus, 0.14 U/kg/hr continuous infusion

–Aim for rate of serum glucose decline of 100 mg/dL/hr

–When glucose 200 mg/dL, reduce infusion to 0.02 to 0.05 U/kg/hr IV or give rapid-acting insulin at 0.1 U/kg SC q2h; goal glucose is 150 to 200 mg/dL.

–Overlap and continue IV insulin infusion for 1 to 2 hours after SC insulin is initiated.

IV fluids to correct dehydration: Start with 0.9% NaCl bolus, calculate

corrected sodium; if serum Na+ is high, consider 0.45% NaCl to replace free fluid loss or when adding potassium replacement.

–When glucose is 200 mg/dL, change to 5% dextrose with 0.45% NaCl at 150 to 250 mL/hr.

Potassium: falsely elevated due to acidosis; when K+ ≤5.2 mg/dLand if urine

output is adequate, start replacement with 20 to 30 mEq/L of K+ in 1 LIV fluids (1).

–Hold insulin if K+ ≤3.3 mg/dL; give IV potassium 20 to 30 mEq/hr with fluids until >3.3 mg/dL to prevent cardiac arrhythmia (class III).

–For each 0.1 unit of pH, serum K+ will change by ~0.6 mEq in opposite

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direction.

Phosphorus: Routine replacement may lead to hypocalcemia; if very low (<1.0), give 20 to 30 mEq/Lof K-Phos in fluids.

Sodium bicarbonate: no demonstrable benefit with a pH >7.0 (2)[B]; rehydration usually leads to resolution of acidosis although some guidelines recommend its use with pH <6.9 or in patients with life-threatening hyperkalemia; however, there is evidence that it may increase cerebral edema, especially in children (3)[A].

Magnesium: If Mg ≤1.8 mg/dLand the patient is symptomatic, consider replacement.

Precautions

–If the patient is on an insulin pump, it should be stopped.

–If glucose does not fall by 10% in first hour, give regular insulin 0.14 U/kg IV bolus and then continuous infusion at previous rate.

–If using bicarbonate, add 100 mmol or 2 ampules of sodium bicarbonate to 400 mLisotonic solution with 20 mEq KCL>200 mL/hr for 2 hours until venous pH is >7.0 and then stop infusion (1).

Second Line

Insulin, SC or IM: Load with 0.3 U/kg SC, followed by 0.1 U/kg/hr; space dosing to q2h once glucose <250 mg/dL; in uncomplicated DKA, may be safe and cost effective (4)[B]

Pediatric Considerations

Children with moderate to severe DKAshould be transferred to the nearest pediatric critical care hospital.

Cerebral edema is a rare complication (~1%) but has a mortality of 20–50%:

–Diagnostic criteria exist for diagnosis; CT may rule out alternative diagnoses.

–Treat with IV bolus of mannitol 1 g/kg in 20% solution, reduce IV fluid rate, and consider hypertonic 3% saline (5).

Geriatric Considerations

Must be careful with impaired renal function or congestive heart failure when correcting fluid and electrolyte abnormalities

Pregnancy Considerations

Pregnancy itself is diabetogenic and also results in a compensated respiratory

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alkalosis (HCO3 19 to 20 mEq/L) with theoretically reduced buffering

capacity.

Pregnant women are more susceptible to DKA.

Euglycemic DKA

Increased risk of preeclampsia and fetal death

β-Tocolytics and corticosteroids can trigger DKA

Perinatal death: 9–35%

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

ADAadmission guidelines: blood glucose >250 mg/dL; pH <7.3; HCO3 ≤15

mEq/L; ketones in urine; ICU setting for severe DKA(6) IV fluids

–1.0 to 1.5 Lover the first hour, then, if serum corrected Na is high or normal, give 0.45% NaCl at 250 to 500 mL/hr depending on hydration state.

–Switch to 5% dextrose in 0.45% saline at maintenance rate when serum glucose <200 mg/dL; maintain blood glucose between 150 and 250 mg/dL.

–Overly rapid correction of fluid balance may precipitate cerebral edema (2) [C]; if the blood glucose level is falling too rapidly, consider using a 10% dextrose solution instead.

Pediatric Considerations

Bolus 10 to 20 mL/kg initially; 4-hour fluid total should be <50 mL/kg to reduce chance of cerebral edema.

Discharge criteria

–Discharge when DKAhas resolved: anion gap <12, glucose <200 mg/dL; pH >7.3; bicarbonate >18 mEq/L; additionally, patients must be tolerating PO intake and able to resume home medication regimen

–Underlying precipitant (e.g., infection) must be identified and treated.

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Patient Monitoring

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Monitor mental status, vital signs, and urine output q30–60min until improved, then q2–4h.

Monitor blood sugar q1h until <200 mg/dL, then q2–6h.

Monitor electrolytes, BUN, venous pH, and creatinine q2–4h.

DIET

NPO initially

Advance to preketotic diet when nausea and vomiting are controlled.

Avoid foods with high glycemic index (e.g., soft drinks, fruit juice, white bread, added sugar, etc.).

PROGNOSIS

DKAaccounts for 16% of all diabetes-related fatalities

Overall DKAmortality of 0.5–2%

In children <10 years of age, DKAcauses 70% of diabetes-related fatalities.

COMPLICATIONS

Cerebral edema (most common cause of death in children with DKA)

Pulmonary edema

Vascular thrombosis

Hypokalemia

Hypophosphatemia

Cardiac dysrhythmia (secondary to hypokalemia or acidosis)

MI, myocardial injury

Acute gastric dilatation

Late hypoglycemia (secondary to treatment)

Erosive gastritis

Infection, mucormycosis

Respiratory distress

REFERENCES

1.Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335–1343.

2.Agus MS, Wolfsdorf JI. Diabetic ketoacidosis in children. Pediatr Clin North Am. 2005;52(4):1147–1163.

3.Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis—a systematic review. Ann Intensive Care. 2011;1(1):23.

4.Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin

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lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med. 2004;117(5):291–296.

5.Watts W, Edge JA. How can cerebral edema during treatment of diabetic ketoacidosis be avoided? Pediatr Diabetes. 2014;15(4):271–276.

6.American Diabetes Association. Hospital admission guidelines for diabetes. Diabetes Care. 2004;27(Suppl 1):S103.

ADDITIONALREADING

American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36(Suppl 1):S11–S66.

Sheikh-Ali M, Karon BS, Basu A, et al. Can serum beta-hydroxybutyrate be used to diagnose diabetic ketoacidosis? Diabetes Care. 2008;31(4):643–647.

SEE ALSO

Diabetes Mellitus, Type 1

Algorithm: Diabetic Ketoacidosis (DKA), Treatment

CODES

ICD10

E10.10 Type 1 diabetes mellitus with ketoacidosis without coma

E13.10 Oth diabetes mellitus with ketoacidosis without coma E10.11 Type 1 diabetes mellitus with ketoacidosis with coma

CLINICALPEARLS

Admit if blood glucose >250 mg/dL, pH <7.3, HCO3 ≤15 mEq/L, and ketones in urine.

Potassium is falsely elevated due to acidosis; start replacement when K+ ≤5.2 mg/dLand urine output is adequate.

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DIABETIC POLYNEUROPATHY

Samir Malkani, MD, MRCP—UK

BASICS

DESCRIPTION

Peripheral nerve dysfunction seen in diabetes; several patterns described (1):

Symmetric polyneuropathy

– Distal sensory or sensorimotor

Mononeuropathy, radiculopathy, and polyradiculopathy

–Cranial neuropathy

–Focal limb or truncal neuropathy

–Radiculoplexus neuropathy (diabetic amyotrophy)

Acute painful small fiber neuropathy

Autonomic neuropathies

Chronic inflammatory demyelinating polyneuropathy (CIDP)

EPIDEMIOLOGY

Prevalence

Generalized polyneuropathy

–10% at diabetes diagnosis

–50% at 10 years

–Cross-sectional prevalence: 15% by symptoms; 50% by nerve conduction

Autonomic neuropathy: 16.7% in a United Kingdom study

ETIOLOGYAND PATHOPHYSIOLOGY

Metabolic derangement due to hyperglycemia

–Aldose reductase converts excess glucose to sorbitol, which causes nerve damage.

–Nonenzymatic glycation of neural proteins and lipids forms damaging advanced glycosylation end products.

–Protein kinase C activation causes vascular endothelial changes.

–Oxidative stress from excessive production of reactive oxygen species

–Cyclooxygenase-2 and poly (ADP-ribose) polymerase activation

Vasculopathy causing nerve ischemia: predominant factor in

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mononeuropathies

RISK FACTORS

Poor glycemic control

Duration of diabetes

Hypertension

Hyperlipidemia

Tobacco and alcohol consumption

GENERALPREVENTION

Maintenance of normal blood sugar Exercise and appropriate diet

DIAGNOSIS

HISTORY

Most common form (typical): symmetric distal sensory or sensorimotor polyneuropathy

–Distressing numbness, tingling, pain of legs/feet, usually worse at night; allodynia; hyperalgesia

–Often silent sensory loss, patient unaware

–Ataxia due to proprioceptive loss

–Neuropathic foot ulcers due to analgesia and repetitive injury

–Neuropathic degeneration of foot joints

–Hands involved late

–Distal muscle involvement, usually mild

Symmetric proximal polyneuropathy

–Proximal leg weakness and wasting

–Muscles of shoulder girdle rarely involved

–Pain and sensory changes less prominent

Focal cranial or limb mononeuropathy

–May involve 3rd, 4th, 6th, or 7th cranial nerve

–Femoral, sciatic, or peroneal neuropathy: weakness or pain in nerve distribution

–Any major peripheral nerve can be involved.

Truncal neuropathies: painful radiculopathy over dermatomes Lumbar radiculoplexus neuropathy (diabetic amyotrophy)

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–Unilateral hip, thigh pain

–Pelvic girdle and thigh weakness with atrophy

–Recovery over months

Diabetic autonomic neuropathy

–GI: nocturnal diarrhea, sometimes alternating with constipation; gastroparesis with postprandial fullness; nausea and vomiting

–Cardiovascular: postural dizziness, exercise intolerance

–Urogenital: urinary hesitancy, overflow incontinence; erectile dysfunction; vaginal dryness; sexual dysfunction

–Sudomotor: anhidrosis or hyperhidrosis; gustatory sweating of head and

upper body

CIDP: progressive, severe motor loss

Diabetic cachexia: painful small fiber neuropathy with prominent weight loss and depression

PHYSICALEXAM

Symmetric distal polyneuropathy

–“Stocking-and-glove” distal sensory loss

–Large-fiber neuropathy: loss of perception of vibration and light touch (10- g monofilament)

–Small fiber involvement: loss of temperature and pinprick

–Absent ankle reflexes

–Wasting, weakness of small muscles in foot; changes to arch of foot or clawing of toes

–With small fiber involvement, there may be lack of objective sensory deficit despite pain.

Symmetric proximal polyneuropathy

–Proximal leg, arm wasting, and weakness

–Loss of patellar reflexes

Focal cranial or limb mononeuropathy

–3rd cranial nerve palsy: painful ophthalmoplegia and ptosis; preserved pupillary reflexes (in contrast to compressive palsies)

–6th cranial nerve: lateral gaze palsy

–Femoral neuropathy: weakness of lower leg extension, hip flexion, quadriceps wasting, absent patellar reflex, sensory loss in anterior thigh

–Sciatic neuropathy: pain or sensory loss in back of thigh and leg; weakness of hamstrings, lower leg muscles

–Peroneal neuropathy: foot drop

Truncal neuropathies: sensory loss along dermatome

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