- Bradycardia & hypotension (most common).
- Myocardial depression & cardiogenic shock (severe overdoses).
- Ventricular dysrhythmias (Common with propranolol & acebutolol).
- Others (mental status change, seizure, hypoglycemia, & bronchospasm).
- Co-ingestions of CCB, TCA, & neuroleptics, increases mortality.
- Mostly symptomatic < 2 hrs following ingestion, & nearly all develop symptoms < 6 hrs.
- Delayed toxicity up to 24 hrs after ingestion (Sustained release meds: metoprolol succinate & sotalol).
- Sotalol prolongs the QTc interval & can lead to Torsades de Pointes.
- Carvedilol (associated with edema & toxic epidermal necrolysis).
- IV lipid emulsion therapy for poisoning involving lipophilic medications (eg, propranolol, metoprolol, labetalol).
Beta-Blocker Overdose/toxicity
QT/QTc- Interval
- Start of Q-wave to end of the T-wave (time of ventricular depolarization + repolarization).
- Life threatening risk of prolonged QTc >500ms = Torsades de pointes (TdP).
- Prolonged QT/QTc interval may be a clue to electrolyte disturbances (hypocalcemia or hypokalemia), drug effects (quinidine, procainamide, amiodarone, or sotalol), or myocardial ischemia (usually with prominent T wave inversions).
- Shortened QT intervals are seen with hypercalcemia and digitalis effect.
- Each 10-millisecond increase in QTc contributes approx a 5% to 7% additional increase in risk for TdP.
- QTc of 540 milliseconds has a 63% to 97% higher risk of developing TdP than a patient with QTc of 440 milliseconds.
- Find a lead with the tallest T wave and count the little boxes from the start of the QRS complex to the point where the T wave comes back down to the isoelectric line.
- Multiply the number of little boxes by 0.04 seconds.
- Example if you counted 8 boxes then QT interval is 8 x 0.04 = 0.32 seconds (320 milliseconds).
- QT interval should be less than half the preceding R-R interval (Works for regular rates between 65-90).
- Bazett formula, QTc = QT / √RR.
- Fridericia formula (QTc = QT / RR1/3)
- Hodges [QTc = QT + 0.00175 x (HR - 60)]
- Framingham linear regression analysis {QTc = QT + 0.154 x (1 - RR)}
- Karjalainen et al. [QT nomogram]
- Rautaharju formula, QTc = QT x (120 + HR) / 180
Rhabdomyolysis
- Rhabdomyolysis is a clinical syndrome that comprises destruction of skeletal muscle with outflow of intracellular muscle content into the bloodstream.
- The systemic complications associated with rhabdomyolysis result from the leakage of muscle intracellular components into the bloodstream.
- Elevated Creatine kinase (CK) hallmark of rhabdomyolysis.
- Defined based on CK values five times above the upper limit of normal.
- Half-life of CK is 1.5 days; elevated<12hrs, peaks in 3 days, & normalizes in 5 days.
- Myoglobin half-life of 2-3 hrs & rapidly excreted by kidneys.
- Rapid & unpredictable metabolism makes myoglobin less useful marker of muscle injury.
- Antibiotics associated with rhabdomyolysis: Daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir.
- Rhabdomyolysis is associated with hyperkalemia, hypocalcemia, hyperuricemia, and hyperphosphatemia.
Management includes appropriate hydration to improve end-organ perfusion, close monitoring of urine output, correction of electrolyte abnormalities, identification of complications like compartment syndrome, and disseminated intravascular coagulation.
Evaluation of Leukocytosis:
Evaluation of Leukocytosis: The term 'leukocyte' applies to any cells within the myeloblast, monoblast, & lymphoid lineages. Include granulocytes (neutrophils, eosinophils, & basophils), monocytes, & lymphocytes (B cells, T cells, and natural killer cells). In adults, leukocytosis often defined as white blood cell (WBC) count > 11 × 109/L.
Mature WBC:
- 80-90% remain in storage in bone marrow.
- 2% to 3% circulate freely in peripheral blood;
- The rest stay deposited along the margins of blood vessel walls or in the spleen
- Life span: 2- 16 days (depending on cell type in the peripheral circulation).
LEUCOCYTOSIS WBC > 11,000 per mm3 [11.0 × 109 per L] Reactive: Typically, 11,000 to 30,000 per mm3. Leukemoid reaction: approx. 50,000-100,000 per (e.g., C difficile infection, sepsis, organ rejection, or solid tumors. Leukemias or myeloproliferative disorders: > 100,000 per mm3. Paradoxical neutropenia: typhoid fever, rickettsia infections, brucellosis, & dengue.
Neutrophil bands
- Immature neutrophils
- Morphologically: absence of complete separation of nuclear lobes with a visible distinction between chromatin & parachromatin in the narrowest segment of the nucleus often flagged on 5-part automated differential & confirmed by PBS.
Leukemoid Reaction: Transient increase in WBC count defined as significant neutrophilia >50x10^9/L in the absence of a myeloproliferative neoplasm. Mature neutrophils seen in a leukemoid reaction. Etiology: sepsis, organ rejection, solid tumors, and bacterial infections. D/D leukemia: increases in blast cells (precursor cells to leukocytes) and immature WBCs, Improves after treating the underlying cause.
Hyponatremia
Para-neoplastic dermatoses (PD)
Para-neoplastic dermatoses (PD):
- Heterogeneous, rare, acquired diseases characterized by the presence of an underlying neoplasia.
- Usually develop simultaneously with the underlying cancer, but they can also occur before or after the development of the neoplasia.
- Their recognition can lead to a prompt cancer detection and to an early start of the appropriate therapy.
Diabetic Ketoacidosis (DKA)
- Serum glucose >250 mg/dL
- Arterial pH <7.3
- Serum bicarbonate <18 mEq/L
- At least moderate ketonuria or ketonemia.
Infection is a very common trigger for DKA in patients who have new-onset diabetes and previously established diabetes. If there is any suspicion of infection, antibiotics should be administered promptly.
2.6% to 3.2% of DKA admissions are Euglycemic Diabetic ketoacidosis (EDKA).
Pregnancy is a risk factor for EDKA because of the physiologic state of hypoinsulinemia and increased starvation.
Alcoholic ketoacidosis may have a similar presentation to EDKA, with anorexia, vomiting, dyspnea, and significant anion gap metabolic acidosis and ketonemia.
Common, early signs of ketoacidosis include nausea, vomiting, abdominal pain, and hyperventilation.
Patients with DKA usually present with a serum anion gap greater than 20 mEq/L (normal 3 to 10 mEq/L). However, the increase in anion gap is variable, being determined by several factors: the rate and duration of ketoacid production, the rate of metabolism of the ketoacids and their loss in the urine, and the volume of distribution of the ketoacid anions.
Continue insulin infusion until ketoacidosis is resolved, serum glucose is below 200 mg/dL, and subcutaneous insulin is begun. Treatment with IV fluid resuscitation should continue until the anion gap closes and acidosis has resolved.
Pemphigus
IgA
pemphigus does not present with oral mucosa blisters. Direct and indirect
immunofluorescence can both help to differentiate PV from IgA pemphigus.
Pemphigus
foliaceus does not affect the oral mucosa and is less common than PV.
Paraneoplastic
pemphigus presents with mucocutaneous vesicles and bullae and can be
differentiated from PV using indirect immunofluorescence and immunoblot.
Zephyr Endobronchial Valve
Key inclusion criteria:
- Severe emphysema: forced expiratory volume in 1 second (FEV1) ≤ 45% of predicted, TLC ≥ 100% of predicted, RV ≥ 150% of predicted
- Resting partial pressure of arterial carbon dioxide (Paco2) ≤ 60 mm Hg
- Resting partial pressure of arterial oxygen (Pao2) on room air ≥ 45 mm Hg
- Body mass index ≤ 31 kg/m2 for men, ≤ 32 kg/m2 for women
- Abstinence from smoking for at least six months
- Completion of pulmonary rehabilitation.
Diabetic foot infections (DFIs)
Most
DFIs are polymicrobial, with aerobic gram-positive cocci, and especially
staphylococci, the most common causative organisms. Aerobic gram-negative
bacilli are frequently co-pathogens in infections that are chronic or follow
antibiotic treatment, and obligate anaerobes may be co-pathogens in ischemic or
necrotic wounds.
Empiric
antibiotic therapy can be narrowly targeted at aerobic gram-positive cocci in
many acutely infected patients, but those at risk for infection with
antibiotic-resistant organisms or with chronic, previously treated, or severe
infections usually require broader spectrum regimens. Imaging is helpful in
most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging
is far more sensitive and specific.
Osteomyelitis
occurs in 15% of ulcers, and 15% of those will go on to require amputation. Approximately
60% of patients undergoing lower extremity amputation have diabetic foot ulcers
as the underlying cause. Following a lower extremity amputation, the 5-year
mortality jumps to 60%.
Surgical
interventions of various types are often needed, and proper wound care is
important for the successful cure of the infection and healing of the wound.
Patients with a DFI should be evaluated for an ischemic foot, and employing
multidisciplinary foot teams improves outcomes.
The
prognosis for a diabetic foot infection depends on many factors including
vascular blood supply and the presence of neuropathy.
Bleeding manifestation
Purpura due to vasculitis is usually palpable and may be pruritic, and the distribution does not follow dependent areas. Wet purpura is the most predictive of serious bleeding in individuals with thrombocytopenia.
Bruise (also called ecchymosis) is caused by the subcutaneous accumulation of extravasated blood. The skin is flat, and the color evolves over time from purplish blue to reddish brown to greenish-yellow, reflecting the metabolism (breakdown) of hemoglobin to biliverdin and bilirubin.
Hematoma is a collection of blood in the extravascular space. Hematomas and hemarthroses (joint bleeding) are typical of coagulation factor deficiencies.
Von Willebrand factor
- Glycoprotein
- Synthesized in endothelial cells & megakaryocytes.
- Excessive bruising & prolonged bleeding
- Levels vary with stress; increase with estrogens, vasopressin, GH & adrenergic stimuli.
- Repeat tests at > 2 weeks
- Type O blood normally has the lowest levels
- Platelet levels tend to be normal, PT should be normal.
von Willebrand disease (Diagnosis)
- VWF antigen level VWF:Ag (Quantity of VWF present in plasma; <50 are considered to be low)
- VWF ristocetin cofactor assay Efficacy of this plasma VWF in its ability to bind platelets in the presence of antibiotic ristocetin.
- Measurement of coagulation factor VIII (FVIII:C)
- Ratio of VWF:RCo/VWF:Ag (differentiate VWD type 1 and 2)
Digoxin (Cardiac glycoside)
Digoxin
(Cardiac glycoside) reversibly inhibits the sodium-potassium-ATPase, causing an
increase in intracellular sodium and a decrease in intracellular potassium. The
increase in intracellular sodium prevents the sodium-calcium antiporter from
expelling calcium from the myocyte, which increases intracellular calcium. The
net increase in intracellular calcium augments inotropy. Cardiac glycosides
also increase vagal tone, which results in decreased conduction through the
sinoatrial and atrioventricular nodes.
Life-threatening
digoxin-induced arrhythmias and other toxic manifestations occur at a substantially
increasing frequency as the plasma digoxin concentration rises above 2.0 ng/mL.
However, toxicity is more likely in the presence of one or more comorbid
conditions (eg, hypokalemia, hypomagnesemia, hypercalcemia, myocardial
ischemia). Hypokalemia is a particularly important risk factor that can promote
digoxin-induced arrhythmias.
PVCs
are often the first sign of digoxin toxicity and are the most common arrhythmia
due to digoxin toxicity. PVCs can be isolated or occur in a bigeminal pattern. The
so-called "digitalis effect" on the ECG consists of T wave changes
(flattening or inversion), QT interval shortening, scooped ST segments with ST
depression in the lateral leads and increased amplitude of the U waves.
Early
recognition of cardiac glycoside toxicity and prompt administration of Fab
fragments is essential for the successful treatment of severe poisoning. Fab
fragments are highly effective and safe and have transformed the management of
cardiac glycoside poisoning.