Grand Rounds Recap 4.22.20
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QiKt: electrolyte abnormalities WITH Dr. gawron and dr. hassani
Calcium
Regulation under hormonal control (PTH, calcitonin and vitamin D)
Biologically active calcium is measured as ionized calcium; total serum calcium in high or low albumin states may not accurately reflect physiologically active calcium
Hypercalcemia
Mild (10.4-11.9), Moderate (12-13.9), Severe (>14)
Clinical manifestations include bone pain, kidney stones, abdominal pain, psychiatric symptoms
>90% is due to primary hyperparathyroid or malignancy
Treatment:
If calcium >10.3, 1) screen for symptoms 2) check for EKG changes (shortened QTc, osborn waves, AV block) 3) send additional labs (BMP, Mg, Phos; consider PTH and thyroid studies)
If calcium 10.3-13.9 with no EKG changes, avoid worsening hypercalcemia (medications - lithium/thiazides, dehydration, inactivity, high calcium diet), consider outpatient workup for hyperparathyroidism
If Ca >14, check iCa. If symptoms are severe or iCa >10, start volume resuscitation and consider calcitonin or bisphosphenate treatment
Volume Resuscitation: start with 1-2L of NS or normosol (LR contains K); goal is euvolemia but most patients require 3-6L in first 24h. Consider starting fluids at 150-200 cc/hr after bolus
Calcitonin: dose = 4u/kg subQ q12 hours; works within several hours but has tachyphylaxis after about 2 days
Bisphosphonates: Use zoledronic acid 4mg IV over 15 min; dose not start working for about 48 hr; avoid in renal dysfunction
Hypocalcemia
Mild/moderate (7.7-8.5; iCa 3.2-4.5), Severe (<7.6; iCa <3.2)
Clinical manifestations include neuromuscular excitation (tetany, cardiovascular complications, fatigue, depression, irritability).
Etiology includes severe inflammation (sepsis, burns), pancreatitis, citrate (massive transfusions, plasmaphoresis, RRT), ethylene glycol poisoning, medications, chronic (hypo-PTH or vit D deficiency)
Treatment:
If calcium <8.6, 1) screen for symptoms 2) check EKG (prolonged QTc, VT, torsades) 3) send additional labs (BMP, Mg, Phos; consider PTH, lipase)
If EKG changes present, 2g IV calcium gluconate over 10-20 min; replace Mg if less than 2
If calcium 7.7-8.5:
chronic hypocalcemia (like from CKD): ensure patient is on PO calcium and vit D
no or mild symptoms: start PO calcium carbonate (1g q12h) and outpatient follow up
severe symptoms; check iCa - 1) if iCa > 3.2, start PO calcium and outpatient follow up 2) if iCa < 3.2, 2g IV calcium gluconate, repeat iCa in 2-3h and if still low repeat and admit
Contraindications to treatment = hyperphosphatemia, ethylene glycol, digoxin toxicity
Potassium
Most of potassium is intracellular. It is excreted through the renal system (90%) and the Gi system (10%).
Multiple things can push K into cells (alkalosis, hypo-osmolarity, insulin, beta agonists) and out (acidosis, hyper-osmolarity, beta blockers, cell lysis)
Hyperkalemia
Causes include pseudohyperkalemia (hemolysis, prolonged tourniquet time, severe leukocytosis/thrombocytosis), hypertonicity (DKA/HHS), medications (ACE, ARB, K sparing diuretics, NSAIDs, beta blockers, digoxin), cell lysis, renal failure, RAAS system malfunction, adrenal insufficiency
EKG changes include peaked T waves, widened QRS, loss of p wave, sine wave, bradycardia, v fib, asystole. Sensitivity of EKG is low, but if you have a high pre-test probability should empirically treat.
Treatment:
If K 5.1-5.5, address underlying cause. PCP or ED follow up in 2 days
If K 5.6-6.4 with no EKG changes, address underlying cause, treat and monitor with gentle kaliuresis and q2-q4 hr labs
If K > 6.5 or EKG changes, address underlying cause, treat with cardiac stabilization, shift and elimination; monitor q2h labs
Cardiac stabilization with 3g calcium gluconate or 1g of calcium chloride
Intracellular shift with10 units insulin regular IV + 20 mg albuterol. If glucose <250 give 2 amps of D50 or 1 amp D50 + infusion. If glucose > 250, monitor.
Elimination options:
Kaliuresis: (must assess volume status)
Isotonic bicarb for hypovolemia + metabolic acidosis
Lasix 40-100mg IV
Chlorothiazide 500-1000mg IV
Acetazolamide 250-500 mg IV
Binders:
Kayexalate is a resin that exchanges Na and K in the Gi system. No strong studies that show it actually works and case reports of colonic necrosis
Patiromer (valtressa) resin that works similar to kaexylate but long duration of action (takes a couple of weeks)
Sodium Zirconium Cyclosilicate (Lokelma) also works similar to kaexylate but about 9x more affinity for K. It is very expensive, but would be dosed 5-10mg
Dialysis
Hypokalemia
Causes reduced intake (anorexia, EtOH abuse), shifts (hypothermia, metabolic alkalosis), medications (insulin, beta agonist, diuretics), extra renal losses (n/v/d, gastric suctioning, diuretics), excess mineralocorticoids, RTA (type I or II), hyperthyroidism.
Presentation includes muscle weakness and cramps, constipation, non-traumatic rhabdo
Treatment targets differ based on underlying diseases: cardiac > 4, cirrhosis >4, renal failure >3-3.5
EKG changes include T wave changes (flattening, inversions, biphasic), ST depressions, U waves, QTc prolongation
Treatment:
Always check Mg and Phos
If K 3.0-3.4, address underlying cause and treat with 40mEq PO. If considering discharge write rx for 10-30 mEq BID. PCP or ED follow up in 2-3 days
If K 2.5-3.0 and no EKG changes, address underlying cause and treat with 20-40 mEq PO +/- 10mEq IV; q2-q4hr labs
If K < 2.5 and EKG changes, address cause and if symptomatic give 20mEq per hour IV and if asymptomatic give 10mEq/hr IV in addition to oral if able to tolerate, closely monitor hourly until stable > 3.0
Taming the SRu WITH dr. Jensen
The Case
Elderly male transferred from OSH who was brought in by family after hearing loud “thud”. Billed as DKA given he had an anion gap acidosis and positive ketones in labs. Arrived intubated, sedated and paralyzed.
Vitals: BP 112/65, HR 126, RR 16, O2 92%, afebrile
Exam: ETT in place, tachycardic, lungs clear, soft abdomen, neuro 1-T-1
Labs: WBC 27.5, BMP with elevated glucose but no anion gap, VBG 7.01/82/21/-11, troponin 0.05
Added on labs concerning for overdose and tylenol came back at 156 and salicylate 76
Diagnosis: Excedrin Migraine overdose
Salicylate Toxicity
Stimulates medullary respiratory center which leads to a respiratory alkalosis and tachypnea on exam
Uncouples oxidative phosphorylation which leads to a metabolic acidosis with hyperthermia, AMS, cerebral/pulmonary edema on exam
Important to note that a normal anion gap does not mean that it can’t be salicylate toxicity (as in the case above)
Mortality rate for salicylate overdose is 3x higher if diagnosis is delayed
Treatment
*Avoid acidemia to decrease distribution and enhance elimination
Sodium bicarb alkalization: normal mental status, pH > 7.35; you can mix 3 amps of bicarb in 1L IVF with goal of 3cc/kg/hr UOP
Hemodialysis: AMS, profound/refractory acidemia, rising level, level >100
Note on intubation: If choosing to intubate, must match prior minute ventilation to avoid hypercarbia.
*Intubation without hemodialysis increases mortality
Acetaminophen Toxicity
Normally 10% of acetaminophen broken down by CYP450 resulting in toxic byproduct NAPQI. Normally this is conjuncted by glutathione to a nontoxic byproduct, but in toxicity your glutathione stores are depleted resulting in hepatotoxicity from NAPQI.
Treatment
N-Acetyl Cysteine: Decreases hepatotoxicity to 5% if given within 8-10 hours
Oral: smells terrible
IV: can cause anaphylactoid reaction - treat with benadryl, steroids, bronchodilators or decrease infusion rate
Toxicity Stages
Hours 0-24: nausea, vomiting, fatigue
Days 1-3: improvement of symptoms, AST/ALT start to rise, RUQ pain near the end
Days 3-4: AST/ALT peak, jaundice, coagulopathy, pain, multi-organ failure
Recovery: Typically will not have chronic liver dysfunction
Pharmacy update: covid medications WITH paige bradshaw, PharmD
Chloroquine and Hydroxychloroquine
Block in vitro viral entry into cells by inhibiting glycosylation of host receptors, proteolytic processing and endosomal acidification
Immunomodularity effects through attenuation of cytokine production and inhibition of autophagy and lysosomal activity in host cells
Two small RCTs in China showed improvement in development of underlying pneumonia, but no difference in virologic clearance
Adverse effects: (<10%) QTc prolongation, hypoglycemia, neuropsychiatric effects, retinopathy
Baseline EKG to evaluate for prolonged QTc recommended
Safe to use in pregnancy
Hydroxychloroquine +/- Azithromycin
Azithromycin does not have in vitro or in vivo activity against COVID-19
Use in combination with HCQ may be beneficial in patients with underlying pneumonia
High risk of clinically relevant arrhythmias limit use and now off recommended medications
Lopinavir/Ritonavir/Darunavir
Approved for treatment of HIV; involved in proteolysis
Showed in vitro activity against other coronaviruses
One small RCT (Cao, et al) evaluating lopinavir/ritonavir showed no difference in primary outcome (time to clinical improvement)
Also lack of evidence to support use of darunavir based treatments
Remdesevir
Inhibition of viral RNA synthesis; investigational drug
Limited availability for use: 1) compassionate use only for children < 18 and pregnant women 2) enrollment in clinical trial
Current data is limited to mainly case reports and case series
Tocilizumab
Monoclonal antibody IL-6 receptor antagonist. IL-6 is key driver of the cytokine storm that can occur in patients infected with COVID-19.
FDA approved for rheumatoid arthritis and cytokine release syndrome (CRS) following chimeric antigen receptor T-cell therapy
Indication: CRS related to COVID-19
Case series of 21 patients associated with clinical improvement in 91% of patients. Improved respiratory function, rapid defervescence and successful discharge. Dose was repeated with 12 hours in 3 patients for continued fever.
RCT currently underway in US
Contraindicated in active TB, ANC <2000, platelets <100,000, AST and ALT > 1.5 upper limit of normal
Recommend obtaining IL-6 prior to initiation, but do not delay therapy pending result
Nitazoxanide
Antiprotazoal agent; suppresses production of proinflammatory cytokines in peripheral blood mononuclear cells; suppresses IL-6 in mice
Currently no known published clinical trial data regarding efficacy or safety in treatment of COVID-19. In vitro activity against various viruses, including coronaviruses and SARS-CoV-2.
Convalescent Plasma
Plasma obtained from patients who have recovered from COVID-19 thought to contain antibodies against SARS-CoV-2. Thought to provide short term passive immunity.
Inclusion criteria used for severe disease and life-threatening disease
Zinc supplementation
Intracellular zinc may impair replication of a number of RNA viruses; chloroquine is a zinc ionophore
ACEi/ARB therapy
Hypothetical harm: human pathogenic coronaviruses bind to target cells through angiotensin-converting enzyme-2 (ACE-2). Expression of ACE2 may be increased in patients treated with ACEi and ARB therapy
Hypothetical benefit: ACEi and ARBs may have a protective effect against lung damage; SARS-CoV-2 down-regulates ACE2 expression such that the enzyme is unable to exert protective effects in organs.
Clinical trial underway where adult patients hospitalized with COVID-19 are started on losartan
Recommended to continue taking these medications if previously prescribed to patients
NSAIDs
Hypothetical harm: speculative link between ibuprofen and increased ACE2 expression leading to worse outcomes in COVID-19 patients
Currently there is no compelling evidence to support an association between ibuprofen and negative outcomes in COVID-19 patients
Corticosteroids
WHO and CDC recommend that corticosteroids not be routinely used in patients with COVID-19 unless indicated for another reason (asthma, COPD, refractory septic shock) or in those who do truly develop concurrent ARDS
quarterly sim WITH Dr. leech
Post Partum Hemorrhage
definition
Greater than 1000 ml of blood loss; >500 makes you suspicious
Hypotension or signs of acute blood loss if unknown EBL
Risk Factors
Prolonged labor
Chorioamnionitis
Differential
Uterine atony (most common cause of PPH), lacerations (do full vaginal inspection), retained placental tissue (sweep uterus), vaginal hematoma, uterine rupture, uterine inversion, placenta accreta, coagulopathy
Management
Oxytocin as soon as baby is delivered
IV - 10-40 units in saline
IM - 10 units
Methergine IM - contraindicated in pre-eclampsia
Hemabate - contraindicated in asthmatics
Misoprostol - can be given SL or rectally
Uterine packing
Foley balloon - use larger Foley with large balloon, inflate with 60 cc of air; multiple catheters can be used
Bakri balloon
Blood products
NRP
Dry, warm, stimulate first
Suction the airway
SpO2 can be very low in first few minutes of life. If hypoxic, administer PPV
Attache EKG leads and goal HR >100
