Case of the Month

Severe Hypoglycemia in a Golden Retriever

Signalment:

9 year old spayed female golden retriever

Presenting complaint:

Found collapsed outside, now having seizures

Presenting History:

The patient was previously diagnosed with diabetes mellitus 3 months prior to presentation. She had been eating normally and had a recent change in her insulin regimen. Her insulin dose was increased from 22 units to 24 units of NPH based on results of blood glucose curves and clinical response. She was pu/pd at 22 units, and drinking and urinating normally 24 units. She had what was described as a hypoglycemic event approximately one month prior to presentation, however when she was tested at that time by her regular veterinarian, her blood glucose was low normal according to her owner. Yesterday, approximately 2 hours after she received her evening dose of insulin, she was panting and was a mildly weak. Her owner gave her some additional food (which she ate well) and the weakness resolved. This morning, she was acting normally and ate well. Her owner gave her the morning dose of insulin. She was observed to be normal during the afternoon, however when the owners came home from work they found her unconscious and non-responsive under a bush. There was no known history of trauma or dietary indiscretion, however she is housed outside and was not supervised for a several hours prior to presentation. She is up to date on her vaccinations and has no other previous pertinent medical history.

Physical exam findings:

Subjective:

Comatose, 3-5% dehydrated. Body condition score: 3/5

Objective:

EENT: pupils miotic but equal and responsive to light. There was some brown material on her tongue (didn’t smell like vomit – r/o dirt).

Heart/lungs: NSF

Lymph nodes: NSF

Skin: NSF

Abdomen/urogenital: NSF

Rectal exam: fine pieces of grass/mulch in her feces

Musculoskeletal: laterally recumbent, otherwise unremarkable.

CNS: comatose, no seizures on presentation. Unable to assess cranial nerves or peripheral nervous system besides reflexes, which were within normal limits

Assessment:

13 year old spayed female golden retriever with historical diabetes mellitus.

Comatose with mild dehydration on presentation

Rule outs:

Hypoglycemic coma

Toxin ingestion

Trauma

Neoplasia (primary CNS vs extra-cranial)

Hypertension

Hypotension

Cardiac arrhythmia

Hypoadrenocorticism

Thromboembolic disease

Infectious (viral, bacterial, parasitic, or fungal) disease

Plan (initial):

Provide flow by oxygen and maintain a patent airway (patient was breathing on her own). Obtain samples to assess blood glucose.

Obtain a complete blood count, biochemical profile, blood gas, and urinalysis.

Hold samples for urine culture, tick titers, toxoplasmosis titers, etc. Monitor blood pressure and cardiac rhythm (continuous ECG). Place intravenous (IV) catheter, initiate IV fluids (and supplemental dextrose as necessary). Monitor level of consciousness. Obtain thoracic and abdominal survey radiographs. Provide supportive care (lubricate eyes and turn frequently while unconscious).

Laboratory diagnostic results and resulting treatments:

Time Blood gluc-ose Mental Status ECG Treatment
0 (10:00pm) 25 Comatose Intermittent VPCs with sinus tachycardia One liter crystalloid bolus, followed by 50 ml 25% dextrose bolus and 15mg diazepam administered intravenously initially; flow by oxygen was administered and a continuous infusion of LRS + 2.5% dextrose at 1.5 times maintenance was started.
0.5hr (10:30pm)   Comatose, seizure and tremor activity noted Ventricular tachycardia Diazepam 15mg IV for initial grand mal seizure activity and then severe facial twitching ( two additional doses were given 5 and 10 minutes after this first dose); Dextrose infusion was increased from 2.5% to 5%
1.5hr (11:30pm) 18 Comatose, seizure and tremor activity noted Ventricular tachycardia Propofol 100mg IV slow bolus given to stop seizure/tremor activity (good response to treatment - resolution of signs); increased dextrose infusion to 7.5% from 5%, an additional 40ml dextrose in 120ml 0.9% NaCl (due to low blood glucose) and 15mg diazepam (due to breakthrough paddling/seizure activity) were given
2hr (12:30am) 29      
2.5 hr (1am) 37 Comatose Ventricular tachycardia An additional bolus of 40ml 50% dextrose diluted with 120ml O.9% NaCl was given
2.6hr (1:10am) 264      
3.1hr (1:40am) 71      
3.5hr (2am) 45     Increased dextrose infusion from 7.5% to 10%; 10mg dexamethasone sodium phosphate and an additional 40ml 50% dextrose diluted with 80ml 0.9% NaCl were administered
4.5hr (3am) 161 Comatose; seizure activity noted Ventricular tachycardia Repeat grand mal seizure occurred and since blood glucose was normal at this point, a propofol CRI was started (0.1mg/kg/minute to start) to treat this; a lidocaine bolus (2mg/kg) was given to try to covert to normal sinus rhythm
5.5hr (4am) 98 Comatose Ventricular bigeminy with intermittent runs of ventricular tachycardia Lidocaine CRI was started at 0.05mg/kg/minute with an initial additional bolus of 2mg/kg lidocaine to reconvert
7.5hr (6am) 158   Ventricular bigeminy  
9.5hr (8am) 50 Comatose to stuporous Rare VPCs Arterial blood gas showed elevated PCO2; propofol CRI weaning was started in an attempt to improve ventilation ability
10.5 hr (9am) 77 Comatose to stuporous Intermittent VPCs with sinus tachycardia  
11.5 hr (10am) 65 Stuporous Rare VPCs Improved PCO2 on arterial blood gas with propofol CRI tapering, no breakthrough seizure activity
15hr (1:30pm) 58 Depressed to stuporous Rare VPCs Continued to decrease propofol CRI (no seizure activity)
17.5hr (4pm) 102   Rare VPCs  
19.5hr (6pm)   Depressed to stuporous Rare VPCs Discontinued propofol CRI
21hr (8pm) 93 Depressed to stuporous normal sinus rhythm On 10% dextrose CRI with LRS, lidocaine CRI (at 0.05mg/kg/min) (as started at 2am and 4am respectively), on nasal oxygen
25hr (11pm) 44 Brief seizure/tremor activity normal sinus rhythm  
26hr (12am) 74 Brief seizure/tremor activity normal sinus rhythm IV bolus of 60mg propofol was administered and she was then restarted on propofol CRI at 0.07mg/kg/minute
31hr (5am) 94 Brief seizure/tremor activity normal sinus rhythm IV bolus of 60mg propofol was administered for breakthrough seizure activity
36hr (10am) 155 Depressed to stuporous normal sinus rhythm Discontinued lidocaine CRI (still on nasal oxygen, propofol 0.07mg/kg/minute and LRS +10% dextrose at maintenance rate)

Overall diagnostic lab work findings as drawn on presentation:

Complete Blood Count

WBC: 15.47 m/mm3 (6.0 - 17.0)

LYM: 0.70 # (1.0 - 4.8)

MON: 0.98 # (2.0 - 10.0)

GRA: 13.78 # (3.0 - 12.0)

LYM%: 4.6 % (12.0 - 30.0)

MON%: 6.4 % (0.1 - 7.0)

GRA%: 89.1 % (62.0 - 87.0)

RBC: 6.86 M/mm3 (5.5 - 8.5)

HGB: 16.6 g/dl (12.0 - 18.0)

HCT: 45.67 % (37.0 - 55.0)

MCV: 67 fl (60.0 - 77.0)

MCH: 24.3 pg (19.5 - 24.5)

MCHC: 36.4 g/dl (31.0 - 34.0)

RDWc: 15.8 (8.0 - 12.0)

PLT: 440 m/mm3 (200 - 500)

PCT: 0.37 %

MPV: 8.5 fl (5.0 - 12.0)

PDWc: 38.4

Diagnostic Profile - *blood drawn prior to any dextrose administration*

ALB: 3.6 (2.5 - 4.4) G/DL

ALP: 88 (20 - 150) U/L

ALT: 109 (10 - 118) U/L

AMY: 550 (200 - 1200) U/L

TBIL: 0.2 (0.1 - 0.6) MG/DL

BUN: 24 (7 - 25) MG/DL

CA++: 10.3 (8.6 - 11.8) MG/DL

PHOS: *1.3 (2.9 - 6.6) MG/DL

CRE: 0.6 (0.3 - 1.4) MG/DL

GLU: *25 (60 - 110) MG/DL

Na+: 151 (138 - 160) MMOL/L

K+: 4.2 (3.7 - 5.8) MMOL/L

TP: 6.9 (5.4 - 8.2) G/DL

GLOB: 3.3 (2.3 - 5.2) G/DL

HEM: 2+, LIP: 1+, ICT: 0


Blood Gas / Electrolyte (IRMA)

Patient Temperature: 102.2


BP: 758 mmHg systolic


Measured @ 37.0 degrees C

pH 7.461

pCO2 28.4 mmHg

pO2 95.0 mmHg


Temperature corrected to values

pH 7.430

pCO2 31.0mmHg

pO2 107.4 mmHg


Measured

Hct 48.6 %

Na+ 149.4 mM

K+ 3.45 mM

iCa 1.13 mM


Calculated results

HCO3- 20.0 mM

TCO2 20.8 mM

BEb -2.4 mM

BEecf -3.8 mM

O2Sat 97.5%

tHb 16.5 g/dL

tHb for BEb 15.0 g/dL

Urinalysis - Method of Collection: urinated and was caught into sterile container

Color: yellow

Turbidity: clear

Specific Gravity: 1.015


Urobilinogen: neg

Glucose: negf

Ketones: neg

Bilirubin: neg

Protein: +300

Nitrite: Neg.

Leukocytes: neg

Blood: LARGE

pH: 7.5


Sediment:


RBC: 30-50 per hpf

WBC: neg per hpf

Bacteria: none seenFat: eg per hpf

Sperm: neg per hpf

Debris: neg per hpf


Casts: none seen


Cells:

Squam. Epith.: g per hpf

Trans. Epith.: nnn per hpf

Renal: n per hpf


Crystals: none seen


Imaging results:


No radiographs were obtained during her hospitalization.

ULTRASOUND REPORT

Primary Concern: Diabetes mellitus

hypoglycemic coma - now stuporous

recurrent refractory hypoglycemia

hypercapnia

mild hypertension (340mmHg initial reading this AM was spurious)

recurrent seizures (even after blood glucose had been stabilized)

cardiac arrhythmias (now only infrequent VPC's - had been much worse overnight), now has intermittent bundle branch block


Date of Ultrasound: Wednesday, September 21, 2005

Area Scanned: Abdomen


Specific Findings:


Liver: The liver is diffusely mildly hyperechoic, rounded and slightly irregular in contour with a few small~1cm hypoechoic nodules.

Gallbladder / Biliary Tract: WNL

Spleen: WNL

Kidneys: ~7cm with a faint hypoechoic subcapsular rim and mildly hyperechoic cortices.

Urinary Bladder: Trace echogenic debris.

Prostate: N/A

GI Tract: The stomach contains a small amount of fluid. The SI are WNL.

Pancreas: The pancreas is visible, mildly hyperechoic with a small ~0.6cm irregular hyperechoic focus and a small ~0.44cm hypoechoic nodule.

Lymph Nodes: None seen.

Reproductive Organs: N/A

Adrenals: 0.6cm WNL.


Diagnostic Impressions: Liver findings are nonspecific R/O changes secondary to DM, steroid hepatopathy or nodular hyperplasia. Biopsy need for a definitive diagnosis. Pancreatic findings are most consistent with previous pancreatitis and nodular hyperplasia. Can not R/O an insuloma but there was no mass visible to support this DDX. Renal changes R/O interstitial nephritis. The hypoechoic outer rim may be the result of fluid therapy.


Ultrasonographer:


Leslie Schwarz, DVM

Diplomate, American College of Veterinary Radiology


Treatment and clinical progression:

For specific treatment, see chart above. Additional supportive care including flow by and nasal oxygen, indwelling urinary collection system, soft bedding, passive range of motion and turning frequently (to reduce the chance of decubital ulcers) and ocular lubrication were also provided.

Outcome: Molly was transferred to a neurology service where she had an MRI which was unremarkable. She continued to make slow progress towards recovery and was eventually discharged to her owners’ care when she was ambulatory but still non-visual. She did continue to have infrequent seizures. She was discharged on a lower dose of insulin and Phenobarbital.

Final diagnosis: Severe hypoglycemic event with lasting neurologic consequences likely secondary to cerebral edema from neuroglycopenia.

Discussion:

Hypoglycemia, whether from insulin overdose (endogenous or exogenous), increased consumption (neoplasia, sepsis or severe polycythemia) or from insufficient production (as seen in pediatric patients, in some sporting breeds, or in patients with liver disease, hypoadrenocorticism, glycogen storage diseases, starvation or portosystemic shunts/liver disease) can cause neurologic consequences such as was seen in this case. Progressive or persistently low serum glucose causes central nervous system vasoconstriction and decreased oxygen delivery in addition to decreased glucose delivery. This causes neuronal dysfunction and eventually neuronal death. The patient may be left with transient or persistent cortical blindness or seizures post-episode.

Patients presenting with a primary complaint of weakness, tremors, disorientation, behavior changes, seizures or coma should have their blood glucose checked on presentation. If the glucose is found to be below 60mg/dl, patients should be offered high protein food (such as Hill’s a/d or Eukanuba Max-Calorie) if they are conscious. An IV catheter should be placed, and 2-4ml/kg of 25% dextrose should be administered intravenously as a bolus. Their blood glucose should be monitored regularly (every hour or more frequently in the emergent period) and the patient should be started on a CRI of dextrose (can be given as part of their fluid requirements as was seen here) to a maximum of 20%. Higher than 25% dextrose given intravenously can cause severe phlebitis therefore should be avoided. If an insulin secreting tumor is suspected, small doses of dextrose given as needed (monitoring the blood glucose with serial testing) should be attempted as large doses may stimulate the tumor causing larger releases of insulin, initiating a vicious cycle. If the patient does not regain consciousness and/or continues to seizure, this may be suggestive of cerebral edema secondary to neuroglycopenia. Additional treatment with mannitol may be necessary if this occurs to reduce further brain swelling. Once a patient has been stabilized, further diagnostics should be done in an effort to determine the etiology of the hypoglycemia.

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