Hypothermia

Elderly male patient with history of mental illness, homelessness, alcoholism, hypopituitarism, hypothyroidism, hypoadrenalism, CVA presents with hypothermia. Patient found submerged in water with head trauma. Received aggressive fluid resuscitation en route. Temperature < 35 C on exam.

• Severity

  • Mild (32.2-35 C): Hypertension, tachycardia, tachypnea, hypovolemia, shivering, ataxia, apathy, increased urine output.

  • Moderate (28-32.2 C): Bradycardia, bradypnea, hypotension, decreased level of consciousness, pupillary dilation, hyporeflexia. No shivering noted.

  • Severe (< 28 C): Non-responsive with non-reactive pupils, apnea, crackles on lung exam, oliguria. EKG shows ventricular arrhythmia, J-waves. Decreased activity on EEG.

• Labs

  • Measure temperature with low-read rectal thermometer

  • Obtain fingerstick glucose, CBC, CMP q4h, PT/PTT/INR, TSH, Free T4, EtOH level, urine drug screen

  • Consider scheduling cosyntropin stimulation test after resuscitation if hypoadrenalism suspected

• Treatment: Do not abandon resuscitation efforts until core temperature > 32.2 C

  • Mild hypothermia and hemodynamically stable moderate hypothermia

    • Remove wet clothing

    • Passive rewarming: Move to warm environment, insulate, administer warmed liquids PO

  • Hemodynamically unstable due to moderate/severe hypothermia

    • Insulate with Bair Hugger, start D5NS at 40 C

    • Avoid NG tube placement due to risk for precipitating AFib

    • Consider surgical c/s for active rewarming via closed thoracic lavage

  • Cardiac arrest

    • Follow AHA resuscitation guidelines, but do not defibrillate unless VFib is present.

    • VFib on EKG: One time trial of defibrillation. If unsuccessful, do not repeat until core temperature > 30 C.

  • Comorbidities

    • Monitor for hemorrhage

    • Replete glucose, electrolytes PRN

    • Suspected alcoholism and/or positive EtOH: Administer empiric thiamine 250 mg IV x 3 days followed by 100 mg PO x 1 month

    • Confirmed adrenal insufficiency: Administer empiric steroid therapy

• Patient advised to prevent future episodes by wearing layers and carrying a winter survival kit

Notes

• Etiology

  • Cold exposure (e.g. homelessness) +/- concomitant alcohol use is the most common cause of hypothermia

  • Hypopituitarism, hypothyroidism, hypoadrenalism, and CVA may result in temperature dysregulation

  • Aggressive hydration is a common cause of iatrogenic hypothermia

• Physiology

  • Severe hypothermia is associated with pulmonary edema (crackles)

  • Cold diuresis: Kidneys lose concentrating ability

  • Hypothermia may disrupt enzymatic reactions in clotting cascade despite normal PT/PTT/INR results

  • Electrolyte levels may change rapidly during resuscitation; this is especially true for potassium

  • J waves are positive deflections occurring at the junction between the QRS complex and the ST segment

• Treatment

  • Most clinical thermometers only measure as low as 34.4C (94F)

  • Core temperature afterdrop: Phenomenon in which pt clinically worsens when circulation resumes and cold blood returns to heart; minimize by utilizing passive rewarming when possible

  • Closed thoracic lavage: Two thoracostomy tubes placed and warmed saline circulated through thoracic cavity

Severe Asymptomatic Hypertension

Patient presents with hypertensive crisis. No subjective complaints. Denies headache, visual disturbance, lightheadedness, nausea, epistaxis, dyspnea, chest pain, palpitations, oliguria. No h/o coronary artery disease, heart failure, CVD, chronic kidney disease, DM, obstructive sleep apnea, EtOH/stimulant abuse. BP >180/>110. RR, SPO2 WNL. No neurologic deficits, JVD, arrhythmia, new onset heart murmur, pulmonary rales on exam.

• Repeat blood pressure 30 minutes after initial measurement

• Blood pressure remains elevated

  • Obtain CMP and compare results to previous labs: Admit to hospital if changes suggest end organ damage, e.g. AKI, AST or ALT > 2x upper limit of normal

  • Outpatient treatment for patients without evidence end organ damage:

    • No h/o HTN: Start home BP monitoring and f/u in 2-4 weeks

    • H/o HTN: Adjust hypertensive medications

Severe HTN with Mild Symptoms

Pt with h/o HTN presents with hypertensive crisis. Reports new onset headache, lightheadedness, nausea, epistaxis, shortness of breath, palpitations, anxiety. BP >180/>110.

• Repeat BP 30 min after initial BP measurement

• Obtain BMP, U/A to assess for end-organ injury; compare with previous labs

• Treatment

  • Agent

    • No h/o asthma, HF, heart block, bradycardia: Administer labetalol 20 mg IV

    • Labetalol contraindicated: Administer hydralazine 10 mg IV

  • Re-evaluate

    • Symptoms improve with short acting HTN Rx: Start/adjust HTN Rx and f/u in 1 week

    • Symptoms do not improve with short acting HTN Rx and no indication of end-organ damage on labs; start/adjust hypertensive tx and f/u in 1 week

    • Concerns about medication adherence and/or evidence of pulmonary rales, JVD, arrhythmia, new onset heart murmur, neurologic deficits: Admit for inpatient management

Notes

• CCASP guidelines

• Systolic > 240 mmHg or diastolic > 130 mmHg may benefit from hospitalization

• End organ damage

  • There is no consensus or guidelines for the definition of end-organ damage criteria in severe hypertension. AKI is commonly considered a marker for end-organ ischemia and the KDIGO definition is provided below. LFT and urine criteria were adopted from preeclampsia management that also assess for end-organ damage.

  • AKI is defined as any of the following:

    • Increase in serum creatinine (SCr) by ≥ 0.3 mg/dl within 48 hours

    • Increase in SCr to ≥ 1.5 times baseline within previous 7 days

    • Urine volume < 0.5 ml/kg/h for 6 hours

White Blood Cells

Leukocytopenia

Pancytopenia

Production

• Iatrogenic, e.g. chemotherapy

• Infection

  • Viral

    • Epstein-Barr virus (EBV)

    • Hepatitis

    • HIV

  • Tuberculosis

• Autoimmune

  • Rheumatoid arthritis

  • Systemic lupus erythematosus

  • Sarcoidosis

• Malignancy

  • Multiple myeloma

  • Leukemia

Consumption

• Splenomegaly (multiple etiologies)

• Disseminated intravascular coagulation

Neutropenia

• Definitions

  • Neutropenia: ANC < 1500 cells/microL

  • Severe neutropenia (ANC < 500): Initiate neutropenic precautions (see below)

  • Agranulocytosis: ANC < 200 cells/microL

• Etiologies

  • Benign ethnic neutropenia (most common)

  • Nutritional deficiency, e.g. B12, folate

  • Viral illness

  • Liver cirrhosis

  • Autoimmune disorder

  • Pancytopenia (see above)

  • Medication-induced, e.g. antibiotics, anti-inflammatories including NSAIDs, clozapine, tricyclic antidepressants, thyroid medications, sulfonylureas

Leukocytosis

Lymphocytosis

• More coming soon

Neutrophilic Leukocytosis

Pt with h/o smoking, irritable bowel disease, hepatitis, rheumatic disease, granulomatous disease, vasculitis, sickle cell s/p splenectomy presents with new onset neutrophilia. Reports recent sick contacts, febrile seizures, panic attacks, surgery. Denies chronic fever, fatigue, weight loss, night sweats, pregnancy. Medications include corticosteroids, beta agonists, lithium, epinephrine, colony-stimulating factors. Fever on exam. No bruising, lymphadenopathy, splenomegaly noted.

• Labs

  • Neutrophils >60% and 7,000/mm^3; obtain repeat CBC to confirm result

  • Obtain peripheral smear

    • Evaluate for hemolytic anemia, ITP

    • Rule out presence of blasts

  • Obtain ESR, CRP, ANA, blood cultures

  • Consider lumbar puncture

• Consider empiric antibiotics

  
  

Notes

• Neutrophilia may be normal in patients with h/o splenectomy, smoking

• Congenital conditions such as Down Syndrome may result in neutrophilia

• Neutrophilia etiologies include physiologic stressors including pregnancy, bone marrow stimulation, acute infection

• Factors that increase concern for malignancy include chronic fever, fatigue, weight loss, night sweats

Monocytosis

• Infectious, e.g. EBV, tuberculosis

• Autoimmune disease

• Chronic myelogenous leukemia

Thrombocytopenia

Pt with h/o alcohol-induced liver disease, leukemia, mechanical heart valve presents with thrombocytopenia. Reports recent tick-bite, fever/night sweats, unintended weight loss, weakness/fatigue, easy bruising. Currently undergoing chemotherapy. Recently received MMR, varicela, and influenza vaccines. Medications include NSAIDs, furosemide, ranitidine. Family h/o thrombocytopenia. Slapped-cheek rash, mucosal petechiae, lymphadenopathy, heart sounds with mechanical click, ascites, hepatosplenomegaly, jaundice on exam. No active bleeding noted.

• Labs

  • Repeat CBC confirms thrombocytopenia

  • CMP shows elevated alkaline phosphatase and AST:ALT >2

  • Obtain blood smear, GGT, hepatitis panel, HIV ELISA

  • Consider obtaining rickettsial viral panel, bone marrow biopsy

• Treatment

  • Stop NSAIDs, furosemide, ranitidine

  • Concern for alcohol withdrawal; start CIWA protocol

  • Platelet count < 50,000/microliter with active bleeding: Transfuse 1 apheresis unit of platelets

• Patient’s hematologist-oncologist notified about current condition

• Counseling

  • Pt advised to stop drinking alcohol

  • Pt counseled that if his condition is medication-induced, it will likely resolve in 7-14 days

Notes

• Risk factors and conditions associated with thrombocytopenia

  • Viral illness including:

    • HIV

    • Hepatitis B/C

    • Parvovirus B19

    • Herpesviridae: VZV, EBV, CMV

    • Tropical: Dengue fever, malaria

  • Alcohol abuse and/or chronic liver disease

    • Mild to moderate thrombocytopenia due to decreased platelet production

    • May be associated with GI bleeding

    • Labs may show macrocytic anemia, elevated AST:ALT, and/or elevated GGT

  • Marrow suppression due to malignancy/chemotherapy: Moderate to severe thrombocytopenia that generally affects all cell lines

  • Congenital thrombocytopenia

  • Iatrogenic

    • MMR, varicella, influenza A (H1N1) vaccines

    • Destruction by mechanical heart valve

• Treatment

  • Repeat CBC to rule out in vitro agglutination

  • Therapy based on platelet counts (per microliter)

    • > 150,000: No further workup

    • 100,000-150,000: Repeat blood work in 2-4 weeks

    • 50,000-100,000: Trend counts until > 100,000 or < 50,000 and attempt to determine etiology

    • < 50,000: Consider hematology referral/consult

Immune (idiopathic) Thrombocytopenic Purpura

• Acquired autoimmune disorder

• Must r/o all other etiologies (see DDX)

• Giant platelets on peripheral smear

• For patient >60 obtain bone marrow biopsy to r/o myelodysplastic syndrome/lymphoproliferative disorders

• Treatment

  • Indicated if acute bleeding is present or platelets <50,000

  • Corticosteroids = first line

  • IVIG and rituximab may also be used

Hypovolemic Hyponatremia - Renal Loss

Pt with h/o intracranial hemorrhage, Addison's disease presents with headache, dizziness, lethargy. Reports anorexia, weakness, fatigue, N/V, abdominal pain, diarrhea, recent diuretic abuse. Tachycardia, orthostatic hypotension, A&O x 3, normal gait on exam; no jaundice.

• Collect blood/urine concomitantly: Obtain BMP, lipid panel, serum osmolality/urea, urine osmolality/sodium/creatinine

• Calculated serum mOsm < 280

• Urine sodium

  • > 40: Diagnosis confirmed

  • Diagnosis unclear due to urine sodium 25-40 mEq/L

    • Infuse 1L isotonic saline

    • Remeasure urine sodium in 1 hour

• Diuretic abuse suspected due to urine fractional excretion urea < 35%

• Schedule morning cosyntropin stimulation test

• Monitor urine; advise MD if output > 100 mL/hr as this may indicate overcorrection

• U/S to evaluate for IVC collapse

• Treatment

  • Correct hyperglycemia

    • Stop diuretic

    • Start NS at maintenance

    • Consider salt tablets for long-term management

  • Obtain endocrine consult

  • Recent seizures or LOC: Consider ICU admission for observation/management

Notes

Etiologies

• Diuretic abuse: Increases urine sodium; use urine fractional excretion of urea if suspected

• Osmotic diuresis due to hyperglycemia

• Addison's disease (anorexia, weight loss, weakness, fatigue)

• Intracranial hemorrhage may lead to salt wasting; consider head CT

Calculations

• Serum mOsm = [(sodium x 2) + (glucose / 18) + (blood urea nitrogen / 2.8)]

• Urine FEU = [(serum Cr * urine urea) / (serum urea x urine Cr)] * 100

Hypovolemic Hyponatremia - Extrarenal

Pt with h/o GI fistula presents with headache, dizziness, lethargy. Reports recent vomiting, constipation, sweating, severe burns. Denies seizures, LOC. Tachycardia, orthostatic hypotension, hyperthermia, A&Ox3 on exam.

• Labs

  • Collect blood/urine concomitantly: Obtain BMP, lipid panel, serum osmolality

    • Calculated serum mOsm < 280

    • Urine sodium < 25

  • Monitor urine; advise provider if output > 100 mL/hr as this may indicate overcorrection

• Imaging

  • U/S to evaluate for IVC collapse

  • Obtain CT to r/o bowel obstruction

• Treatment: Administer isotonic or hypertonic saline

Notes

• Etiology

  • Vomiting/diarrhea may lead to GI sodium loss

  • Bowel obstruction → third spacing → hyponatremia

• Serum mOsm = [(sodium x 2) + (glucose / 18) + (blood urea nitrogen / 2.8)]

Diet-Induced Euvolemic Hyponatremia

Elderly pt with h/o schizophrenia, alcoholism presents with new onset headache, lethargy, dizziness. Reports anorexia, excess beer and water consumption. Diet consists of tea and toast. No orthostatic hypotension, moist mucous membranes, no LE edema on exam.

• Obtain BMP, urine sodium/osmolality/drug screen, EtOH level

  • Serum mOsm < 280

  • Urine Na > 40 mEq/L and urine osmolality < 100 mOsm/kg

• U/S shows no IVC collapse

• Treatment

  • Regular diet and restrict fluid to 500 mL less that daily urinary output; start 1.5 L fluid restriction

  • Suspected EtOH abuse: Start CIWA protocol and treat accordingly

  • Psychogenic polydipsia

    • Obtain EKG; restart previous psychiatric medications if QTc WNL

    • 1:1 sit and monitor while showering

• Consider social work, case management consult

Serum mOsm = [(sodium x 2) + (glucose / 18) + (blood urea nitrogen / 2.8)]

Hypernatremia

Elderly pt on hemodialysis with h/o altered mental status, DM, diabetes insipidus, and salt tablet/diuretic abuse presents with new onset vomiting, watery diarrhea, polyuria and diffuse burns. Additional symptoms include anorexia, muscle weakness, restlessness, N/V. Febrile with hyperventilation on exam.

• Obtain CMP, TSH serum osmolality, urine sodium, urine osmolality, urinary uric acid

  • Corrected Na = measured Na + 0.024 × (serum glucose − 100)

  • FENA = ([Plasma Cr × urinary Na] / [plasma Na × urinary Cr]) × 100

• Low threshold for head CT as hypernatremia can cause brain shrinkage with concomitant vascular rupture/intracranial bleed

• Treatment

  • Hold amphotericin, aminoglycosides, lithium, phenytoin (Dilantin)

  • Concern for impaired thirst mechanism due to decreased PO intake; pt encouraged to increase PO intake

Notes

• Hypernatremia is associated with increased morbidity/mortality in the inpatient setting

• FENA interpretation

  • Prerenal < 1%

  • Intrinsic > 1%

  • Postrenal > 4%

Stress Hyperglycemia

Pt with h/o DM presents with transiently elevated blood glucose. Recent h/o CNS infection, sepsis, and ICU admission. Current temperature > 39 C.

• D/c glucose containing fluids

• Titrate insulin to maintain blood glucose of 140-180

Acid-Base Disturbances

Initial Approach

1. What is the primary derangement and is it metabolic or respiratory?

   • Acidosis = pH < 7.35

     • Respiratory: pCO2 > 40

     • Metabolic: pCO2 < 40

   • Alkalosis = pH > 7.45

     • Respiratory: pCO2 < 40

     • Metabolic: pCO2 > 40

2. Is the primary derangement acute/chronic and adequately compensated?

   • Clinical assessment and a blood gas (arterial or venous) are needed to determine etiology and degree of compensation

   • Respiratory acidosis

     • Acute

       • Δ PaCO2 of 1 → Δ pH 0.01

       • For every ↑ 10 mEq PaCO2 = ↑ 1 mEq HCO3

     • Chronic: For every ↑ 10 mEq PaCO2 = ↑ 3-5 mEq HCO3

   • Metabolic acidosis: Expected PaCO2 = (1.5 x HCO3) + 8 +/- 2

     • If measured PaCO2 is higher than expected, then respiratory compensation is inadequate, i.e. respiratory acidosis.

     • If measured PaCO2 is lower than expected, it implies underlying respiratory alkalosis.

   • Metabolic alkalosis: Expected PaCO2 = (0.7 x HCO3) + 21 +/- 2

     • If measured PaCO2 is higher than expected, it implies acute respiratory acidosis, i.e. inadequate respiratory compensation.

     • If measured PaCO2 is lower than expected, it implies underlying respiratory alkalosis.

Respiratory Acidosis Etiology

• Central nervous system depression

  • Acute: Trauma, intoxication, encephalitis

  • Chronic: Neuromuscular disease, e.g. muscular dystrophy

• Lung disease

  • Asthma/COPD exacerbation

  • Pneumonia

  • Pleural effusion

Metabolic Acidosis Etiology

Anion gap

• [Na+] - ([Cl-] + [HCO3-])

• Normal anion gap ≈ 12

High Anion Gap Metabolic Acidosis (HAGMA): MUDPILES

• Methanol

• Uremia

• DKA

• Paraldehyde

• Iron, INH toxicity

• Lactic acidosis

• Ethanol, ethylene glycol

• Seizure, starvation, salicylates (aspirin)

Normal Gap Metabolic Acidosis: USED CAR

• Urinary-colonic fistula

• Saline

• Endocrine disorders of aldosterone, e.g. Addison’s disease

• Diarrhea

• Carbonic anhydrase inhibitor, e.g. acetazolamide

• Alimentary (total parenteral nutrition)

• Renal tubular acidosis

Etiology per Pathophysiology

• HAGMA due to increased acid ingestion/production

  • Lactic acidosis

    • Hypoxia including hypovolemic, cardiogenic, and distributive (septic) shock

    • Systemic disease, e.g. cirrhosis, malignancy

  • Ketoacidosis: Starvation, Alcohol, DM (ketoacidosis = SAD)

  • Acid ingestion: Methanol, ethylene glycol, salicylic acid (aspirin)

• Normal anion gap metabolic acidosis: HCO3 versus H+

  • Bicarbonate: Decreased production or increased elimination

    • Diarrhea

    • Carbonic anhydrase inhibitors

    • Type 2 (proximal) renal tubular acidosis

  • Decreased renal acid excretion

    • Chronic kidney disease

    • Renal tubular acidosis types 1 and 4

Additional Calculations

• Osmolar gap = Measured serum OSM - [2(Na+) + (glucose/18) + (BUN/2.8)]

  • Normal ≈ 10 to 15

  • Used to help further differentiate HAGMA etiology in cases of toxic ingestion

    • > 10 to 15 but < 25 indicates alcohol toxicity, e.g. methanol, ethanol, ethylene glycol, propylene glycol, isopropyl alcohol

    • > 25 indicates methanol or ethylene glycol

• Urine anion gap = [(urine Na)+(urine K)] - urine Cl

  • Normal ≈ 0

  • Negative balance indicates gut losses

  • Significantly elevated balance indicates chronic kidney disease or renal tubular acidosis

Acidosis Management

Metabolic

• Treat underlying etiology: DKA, lactic acidosis (shock/cirrhosis/malignancy), diarrhea, CKD, toxic ingestion

• Severe acidosis (pH < 7.1)

  • Transfer patient to ICU and assess for intubation

  • Initiate sodium bicarbonate at 50 to 100 mEq per day and titrate to pH > 7.3

Respiratory (hypercapnia)

• Treat underlying etiology

  • Common: Asthma, COPD, PNA

  • Additional considerations: Trauma (e.g. tension pneumothorax), toxic ingestion (e.g. opioids), pleural effusion

• Hypercarbia/CO2 narcosis in patient with altered mental status, RR > 25, and/or pH < 7.3:

  • Initial evaluation

    • Consider contributing etiologies (see above)

    • Note: Altered conscious does not usually occur until PaCO2 > 75 mmHg

  • Start BiPaP 12/5 at 30% FiO2

    • Increase FiO2 by 5% every 10 minutes to achieve to SPO2 90-93%, i.e. FiO2 30% → 25% → 40% → etc.

    • If pt cannot tolerate BiPaP, transfer to ICU for sedation and monitoring

  • Provided continued hemodynamic stability, recheck ABG after 1 hour if significant clinical improvement is noted

  • Intubate for any of the following

    • Development of hemodynamic instability

    • No significant improvement of clinical status and ABG values after 1 hour

• Intubate for pH < 7.2

Alkalosis

Common Etiologies

• Metabolic

  • Diuretic therapy

  • Gastric secretion loss (vomiting)

• Respiratory

  • Acute: Hyperventilation (multiple respiratory etiologies)

  • Chronic: Pregnancy, heart failure, hepatic failure, hyperthyroidism

• Treatment

  • Address underlying etiology, e.g. stop diuretics, control nausea, etc.

  • Consider administration of one of the following:

    • Potassium chloride if hypokalemia is present

    • Acetazolamide (carbonic anhydrase inhibitor) 500 mg IV x 1 dose

Hypercalcemia

Pt with h/o nephrolithiasis presents with lethargy/weakness, abdominal pain, flank pain, and confusion. Reports recent, excessive intake of vitamin D, calcium, and thiazide diuretic. Family history positive for sarcoidosis, breast cancer. HTN, irregular heartbeat, abdominal tenderness, flank pain, muscle weakness, and lower extremity edema on exam.

• CMP shows corrected calcium > 10.5 mg/dL

  • Repeat CMP and re-evaluate serum calcium and creatinine levels

  • If repeat serum calcium elevated; obtain PTH level and serum ionized calcium

• Obtain PTH level

  • PTH > 65 pg/mL: See primary hyperparathyroidism

  • PTH < 20 pg/mL: Obtain PTHrP, 1,25-dihydroxyvitamin D, and 25-dihydroxyvitamin D levels

    • Elevated PTHrP: Obtain CBC, and consider CXR, mammogram, abdominal CT, and/or serum electrophoresis

    • Elevated 1,25-dihydroxyvitamin D: Obtain CXR to r/o sarcoidosis, lymphoma

    • Elevated 25-dihydroxyvitamin D levels: Review all medications and counsel pt about vitamin D toxicity.

    • All levels normal: Consider obtaining TSH, serum protein electrophoresis, cortisol level, and/or vitamin A level

• EKG shows peaked T waves

• Treatment

  • Calcium < 14 mg/dL: Stop vitamin D, calcium supplementation and thiazide diuretic; encourage adequate hydration

  • Calcium > 14 mg/dL

    • Start normal saline at 250 mL/hr and adjust to maintain urine output of 100 mL/hr

    • Consider starting once-monthly pamidronate 90 mg IV

Notes

• Corrected Ca = [0.8 x (normal albumin - patient's albumin)] + serum Ca level

• PTHrP = Parathyroid hormone related peptide

• Resources: https://clinicalproblemsolving.com/dx-schema-hypercalcemia/, https://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia

Notes

• Nodules <4 mm in patients age 65 years or younger with no history of smoking or malignancy may not need follow-up imaging. The algorithm above provides a simplified and cautious approach.

• Link: Solitary pulmonary nodule malignancy risk calculator