Pediatric Respiratory Illness

Case Presentation

!  24 y/o mother brings in her 9 month old child. She states that he seems to have a slight cough and he “just isn’t acting right”. He is more sleepy and fussy than usual.

!  Sick contacts at daycare

!  Missing 6 month immunizations, o/w UTD

!  ? Fevers. No diarrhea. Maybe some vomiting, she attributes that to his reflux. Seems to be eating ok. Normal or increased amount of diapers.

Your Patient

Vital signs

!  Wt 10 kilos, he is screaming at triage when vitals are taken. He readily calms and drinks from the bottle. He has a moderate sized snot bubble in the right nares.

!  HR – 159

!  RR – 56

!  Cap refill ~ 2 sec, sat is 99%

History

!  What other questions do you have?

!  FHX: ?

!  Birth hx?

!  Sick contacts?

!  Immunizations?

Physical Exam

!  Pertinent positives:

!  Slight nasal crusting – clear

!  RR seems increased, slight retractions, no wheezing heard.

!  Tachycardia at 149 on your exam, but he is crying

!  Abdominal exam – normal except a small reducible umbilical hernia.

You find this rash (what is it?):

Differential Diagnosis:

Lab Tests?

!  RSV wash?

!  CBC?

!  Lytes?

!  UA/urine culture?

!  Blood cultures?

!  CXR?

Work Up:

Patient Dispo

Goals and Objectives

!  Recognize DKA, especially new onset

!  Select correct lab studies

!  Fluid and insulin treatment

!  Cerebral edema

Pediatric DKA !  International Society for Pediatric and Adolescent

Diabetes (ISPAD) in 2007 defined:

!  Hyperglycemia: glucose > 200 mg/dL AND

!  Metabolic acidosis: venous pH < 7.3 and/or plasma bicarbonate < 15 mEq/L.

!  Severity categorized according to the degree of acidosis: mild (pH 7.2-7.3), moderate (pH 7.1-7.2) and severe (pH < 7.1)

!  DKA leading cause of morbiity/mortality in children with type 1 diabetes.

!  Clinical manifestations related to degree of hyperosmolality, volume depletion, and acidosis.

DKA v Hyperosmolar Hyperglycemic State

!  Marked hyperglycemia: > 600

!  Serum CO2 > 15 mmol/L

!  Absent to mild ketonemia and ketonuria

!  Effective serum osm >320

!  Usually in adults but has been increasingly seen in adolescents. Still not common in the younger child.

!  Associated with more severe hypotension and dehydration than DKA.

Epidemiology !  DKA is frequently the initial presentation of children with

new onset type 1 DM.

!  Factors associated with increased risk for DKA at presentation: !  Younger age ( < 5 y/o) – population study Germany –

higher incidence of DKA in <5 36% vs 26% of older children

!  Ethnic minority status

!  Diagnostic error

!  Lack of health insurance

!  Lower body mass index

!  Delayed treatment

DKA in type 1 DM

!  Risk/predictive factors for recurrent DKA: ! Higher A1C values ! Higher reported insulin requirements !  Female adolescents >13 y/o ! Children over 13 y/o (regardless of

gender) who have no insurance and/or have psych issues

!  Longer duration of DM

DKA !  Almost 60% of DKA episodes occur in ~ 5% of

children.

!  Patients with dm who had 4 or more episodes = 35% of all episodes of DKA in a UK surveillance study.

!  Less common BUT ketosis and DKA can occur in type 2 DM.

DKA – Precipitating Factors

!  Poor metabolic control

!  Frequently missed insulin

!  Stress and infections

!  Medications: corticosteroids, etc

Signs and Symptoms

!  Sxs/sxs related to the degree of hyperosmolality, volume depletion, and acidosis.

!  Earliest sxs related to hyperglycemia

!  Older children: polyuria, polydipsia, fatigue, wt loss, nocturia, vaginal or cutaneous moniliasis.

!  Infants: More difficult – not toilet trained and can NOT express thirst. SXS: decreased energy and activity, irritability, weight loss, and physical signs of dehydration. Candidal diaper rash common.

Signs/Symptoms Continued

!  Polyphagia – early. As ketoacidosis worsens, appetite is suppressed. +/- abdominal pain, N, V

!  Hyperventilation and deep respirations – respiratory compensation for acidosis.

!  Children with DKA are volume depleted, but less likely to show classic signs of hypovolemia.

!  Neurologic findings: drowsiness, lethargy, and coma – related to severity of hyperosmolality and/or the degree of acidosis.

!  Cerebral edema: 0.5-1% of all DKA cases in children

DKA – fluid deficits

!  Most studies of fluid needs were done in the 40’s and 50’s on adults. Fluid losses in severe pediatric DKA: !  Water – 70 mL/kg

!  Sodium – 5-13 mEq/kg

!  Potassium – 6-7 mEq/kg

!  Fluid losses more difficult to assess in pediatric DKA

!  Generally present with a 5-10% fluid deficit.

!  Initial fluid management is based on the assumption of a 5-7% deficit for moderate and 10% for severe.

Volume

! Consensus: the maximal volume of isotonic solution used for initial treatment is 10 - 20 mL/kg unless the patient is objectively hypotensive.

Lab Testing

!  Initial labs: !  Serum glucose

!  Electrolytes

!  Creatinine and BUN

!  Blood gases

!  Hematocrit

!  BHOB

!  Urine testing – ok for initial test but may give false impression of continued ketoacidosis – use direct measurement of BHOB.

Anion Gap

!  Anion gap is useful for estimating the severity of ketosis.

!  Normalization is a direct measure of the resolution of ketoacidemia.

!  May underestimate the degree of acidosis.

!  Calculated:

!  Serum AG = Serum Na - (Serum Cl + bicarb)

!  Normal pediatric value: 12 +/- 2

Sodium

!  Affected by hyperglycemia

!  Hyperglycemia ! increase in plasma osmolality ! water movement out of cells ! lower serum Na (by dilution)

!  Theoretical calculations: decrease in serum Na by 1.6 for every 100 mg/dL elevation in serum glucose. Am J of Med, Hiller, et al suggest better estimate is a reduction of 2.4 mEq/L for every 100

Sodium

!  Inability to independently access water in infants and young children may lead to hypernatremia despite the hyperglycemia.

Potassium

!  Osmotic diuresis and Increased ketoacid excretion promote urinary loss of K+.

!  K+ loss in adults (on average) 3-5 mEq/kg

!  K+ loss in pediatrics (less well studied): 6-7 mEq/kg.

!  If hypokalemic at presentation, delay insulin therapy until K+ repletion begins.

Serum Bicarb

!  Study at the University of Oregon – looking at serum bicarb as a predictor of pH. 300 + patients enrolled. !  Serum bicarb of 18.5 or less – predicts pH < 7.3,

sensitivity – 93%, specificity – 91%

!  Serum bicarb of 10.5 or less predicts pH of < 7.1, sensitivity – 97%, specificity – 88%

!  Conclusion: venous pH may not be necessary in children.

DX

!  Glucose: serum glucose - >200

!  Acid-base: bicarb < 15 mEq/L or venous pH < 7.3 The severity of metabolic acidosis is dependent on: !  Rate of ketoacid production

!  Duration of increased ketoacid production

!  Rate of acid excretion in the urine

!  The adequacy of the compensatory respiratory alkalosis.

Back to our patient:

!  Labs: glucose 330

!  Na+ - 130

!  K+ - 3.7

!  Cl- - 98

!  HCO3 – 9

!  BUN – 19

!  Cr – 1.9

!  Concerns? Plan for care?

Our patient has:

!  Hyperglycemia

!  Acidosis

!  Relative hypokalemia

!  Dehydration

!  Renal insufficiency

!  Candidal diaper rash

!  Anything else you really want to know right now?

Neurologic Exam

!  Neurologic compromise at presentation is a poor prognostic indicator.

!  Retrospective study, 61 peds pts with DKA and cerebral edema: !  All who died or were persistently vegetative

presented with GCS < 7

!  High morbidity and mortality – need to recognize and treat

!  MORE TO COME later

Back to our patient:

!  He seems neurologically intact.

!  What are your plans now? !  DKA

!  Dehydration

!  Renal insufficiency

!  Relative hypokalemia

!  Candidal diaper rash

!  Fluids??? Insulin??? Treatment for cerebral edema

Peds DKA Tx

!  The approach and principles of management are essentially the same for all children in DKA.

!  Treatment plans will be guided by severity.

!  European Society for Pediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society (ESPE/LWPES) have set forth guidelines.

!  In the past MULTIPLE ways and guides to treatment for DKA

Peds DKA Treatment

! The consensus from multiple societies is that the treatment protocol should be simple and relatively standardized to decrease errors in management

Goals of Therapy

!  Correct dehydration

!  Correct the acidosis and reverse ketosis

!  Restore blood glucose to near normal

!  Avoid complications of therapy

!  Identify and treat any precipitating event.

Fluids

!  First assess for dehydration.

!  At best, the clinical assessment is imprecise.

!  3 most useful clinical signs: !  Prolonged capillary refill

!  Abnormal skin turgor

!  Hyperpnea

!  > 10% ! weak peripheral pulses, hypotension, and oliguria

Fluids

!  Usually there is a deficit in extracellular fluid volume in the range of 5-10%.

!  Shock with hemodynamic compromise is relatively rare in pediatric dka.

!  Clinical estimates of deficit are subjective and inaccurate, therefore: !  Moderate DKA: 5-7%

!  Severe DKA – 7-10%

Goal of fluid & electrolyte replacement therapy:

!  Restore circulating volume

!  Replacement of sodium and ECF & intracellular fluid deficit of water.

!  Improved glomerular filtration with enhanced clearance of glucose and ketones

!  Reduce the risk of cerebral edema

Fluids

!  Fluid repletion should be done gradually and with isotonic fluids.

!  Evidence of fluid resuscitation and cerebral edema is not conclusive either way.

!  General consensus: initial volume expansion – is 10 ml/kg to be given over the first hour.

!  May give a second bolus of 10 cc/kg IF hemodynamically compromised.

! DO NOT give more than 20 cc/kg, unless unstable.

What fluid to use? !  NS for initial boluses

!  K+??? !  If K+ is elevated, may wait until you get cr back

!  If K+ is normal, add when the child urinates or with the initiation of insulin therapy

!  If K+ is low, add immediately

!  Do not begin insulin therapy with severe hypokalemia

!  It is added to the maintenance fluids.

!  Rate of fluids should then be 1.5-2 times maintenance.

!  Do not need to replace urinary fluid losses.

!  Continue NS or LR for first 4-6 hours (???)

SUMMING UP FLUIDS

!  10 – 20 cc/kg bolus

!  NS +/- K at 1.5 – 2 times maintenance

!  Change to ! normal about 4 hours into it, ?earlier, ? Younger child

!  Don’t exceed these rates unless patient is in extremis.

!  Easy, right?

Insulin

!  After the first bolus is complete, initiate insulin.

!  0.1 unit/kg/hour

!  For younger children (usually <3) the rate should be 0.5 units/kg/hour.

!  NO BOLUS!!!!!!

!  Study in Germany – less complications with low dose insulin 0.025 u/hr. Resolution took longer.

!  Mix insulin with NS, 1 unit/ml and give on syringe pump to decrease extra fluids.

Insulin continued

!  If serum glucose decreases to <300-250 and the ketoacidosis is not corrected, change the iv to D5NS or D5LR.

!  It is recommended to have serum glucose levels around 150-200 for younger children and 100-150 for older kids.

Sum it up again

!  10-20 cc/kg fluid bolus NS

!  Maintenance – 11/2 to 2 times

!  K+: if low, give K+ and delay insulin therapy, K+ normal -add K+ when tx begins, high – begin therapy follow K+, initiate K+ when K+ is lowered and when child has urinated.

!  Insulin: 0.1 u/kg/hr or 0.05 units/kg/hour (<3)

!  Monitor for cerebral edema

Bicarb??

!  There is substantial evidence that bicarbonate therapy should not be used in DKA

!  Risks from bicarb therapy: !  Excess NaHCO3 tx can lead to a paradoxical fall in

cerebral pH

!  Administration of alkali may slow the rate of recovery of ketosis

!  Can lead to a post-tx metabolic acidosis

!  ADA & ESPE/LWPES “selective pts may benefit from NaHCO3 – severe acidemia – pH < 6.90

Monitoring !  Monitor glucose hourly during the initial 4-6 hours.

!  Electrolytes and venous pH initially evaluated hourly for the first 3-4 hours, then q 2

!  Monitor vs

!  Monitor for signs of cerebral edema

Subcutaneous Insulin?

!  Younger children (sensitive to insulin) should be hospitalized.

!  Venous pH > 7.30, no neurologic impairment, and volume deficit estimate of < 3%. – can do regular insulin q 3-6 hours.

!  Inhaled insulin – on the horizon

Neurologic Eval – cerebral edema

!  Major Criteria !  Altered mentation/fluctuating LOC

!  Sustained HR decel (>20 bpm)

!  Age inappropriate incontinence

!  Minor Criteria !  Vomiting, HA

!  Lethargy or being not easily aroused from sleep

!  Diastolic BP > 90 mmHg

!  Age < 5 years.

Cerebral Edema !  Diagnostic criteria

!  Abnormal motor or verbal response to pain

!  Decorticate or decerebrate posture

!  Cranial nerve palsy (most notably – III, IV and VI)

!  Abnormal neurogenic respiratory pattern: !  Grunting

!  Tachypnea

!  Cheyne-stokes respiration

!  apneusis

Cerebral Edema

!  Diagnosed if ANY diagnostic criteria present

!  With two major criteria

!  With one major and two minor criteria

Cerebral Edema

!  The incidence is 0.5 – 0.9% of DKA episodes

!  Mortality rate 21-24%

!  Pathogenesis unclear. Increased risk factors: !  Younger age

!  New onset diabetes

!  Longer duration of symptoms

Cerebral Edema

!  Factors present at time of presentation that increase risk of cerebral edema: !  Greater hypocapnia

!  Increased serum nitrogen (may represent a greater degree of dehydration)

!  More severe acidosis

!  Bicarbonate therapy

!  Attenuated rise in measured serum sodium concentrations during therapy

!  Administration of insulin in the first hour of fluid treatment.

Cerebral Edema

!  Glaser, et al published in 2006, Pediatric Diabetes Journal. 41 children in DKA had MRI’s done: !  Lateral ventricles were significantly smaller during

treatment than afterwards.

!  56% of children had ventricular narrowing during treatment – these children were more likely to have mental status changes than those without narrowed ventricles.

Pathophysiology

!  Cause of cerebral edema is not fully understood.

!  Only way to definitively prevent it is to avoid DKA.

!  May be present before the initiation of treatment, but more commonly presents 4-12 hours into treatment.

Proposed Mechanisms

!  Ischemic/cytotoxic edema: MR spectroscopy have shown a decrease of N-acetylaspartate (NAA) – a marker of neuronal function/viability.

!  Vasogenic edema: primary damage to the cerebral vascular endothelium!increased blood-brain barrier permeability or a disturbance in autoregulation.

!  Osmotic edema secondary to fluid tx: osmotic pressure promotes water movement into the intracellular compartment. During tx, insulin and fluid repletion lowers the serum glucose and plasma osmolality ! promoting osmotic water movement into the brain.

Cerebral Edema

!  By the time the diagnostic criteria develop, cerebral edema is already advanced: !  Abnormal motor or verbal response to pain

!  Decorticate or decerebrate posture

!  Cranial nerve palsy (III, IV, and VI)

!  Abnormal neurogenic respiratory pattern

Treatment

!  Essential part of DKA tx is monitoring for changes.

!  Decrease rate of fluids

!  Mannitol: 0.25 – 1.0 g/kg IV over 20 minutes – based only on case reports. Retrospective study – no benefit.

!  3% saline – 5-10 ml/kg over 30 minutes

!  Intubation/ventilation – No hyperventilation. Poor outcome with pCO2 <22

Case Review

!  10 month old with URI symptoms – tachypnea is seemingly out of proportion to his illness.

!  Lab shows elevated AG, glucose and a decreased bicarb., initial K+ is 3.7.

!  What is your treatment plan ?

Treatment Plan

!  IV fluid bolus: ns 10 cc/kg – 100 cc bolus over one hour. Does he need a repeat?

!  IV – after initial bolus, NS at a rate of 1.5-2 times maintenance (4-2-1 rule), add K+

!  IV insulin – what rate for this child?

!  Monitor neuro status and transfer to pediatric institution.

Take home points!!!

!  Bolus NS – do not exceed 20 cc/kg unless unstable – Do not volume overload.

!  Continue NS for the first several hours

!  Add insulin after one hour – 0.1 units/hour or 0.05 units/kg if less than 3 y/o

!  Monitor glucose every hour. Monitor lytes, ag and bhob every hour for the first 3-4 hours. Should you have the patient longer, go to q 2.

!  Monitor for cerebral edema.