Friday, October 10, 2014

Acid-Base disturbances. Physiological Approach

This has been one of those topics that give me a headache. However, having a simple approach is very helpful. This week's NEJM (Oct 9th) has an interesting review. Here are the Q&A on this topic.

What are some uses and limitations of the anion gap?
Lactic acidosis accounts for about half of the high anion gap cases, and is often due to shock or tissue hypoxia. The anion gap however, is a relatively insensitive reflection of lactic acidosis — roughly half the patients with serum lactate levels between 3.0 and 5.0 mmol per liter have an anion gap within the reference range. With a sensitivity and specificity below 80% in identifying elevated lactate levels, the anion gap cannot replace a serum lactate measurement. Nevertheless, lactate levels are not routinely drawn or always rapidly available, and a high anion gap can alert the physician that further evaluation is necessary. In addition, the anion gap should always be adjusted for the albumin concentration, because this weak acid may account for up to 75% of the anion gap. Without correction for hypoalbuminemia, the anion gap can fail to detect the presence of a clinically significant increase in anions (>5 mmol per liter) in more than 50% of cases. For every 1 g per deciliter decrement in serum albumin concentration, the calculated anion gap should be raised by approximately 2.3 to 2.5 mmol per liter.
What are the characteristics of a normal anion-gap (hyperchloremic) acidosis?
Chloride plays a central role in intracellular and extracellular acid–base regulation. A normal anion-gap acidosis will be found when the decrease in bicarbonate ions corresponds with an increase in chloride ions to retain electroneutrality, also called a hyperchloremic metabolic acidosis. This type of acidosis occurs from gastrointestinal loss of bicarbonate (e.g., because of diarrhea or ureteral diversion), from renal loss of bicarbonate that may occur in defective urinary acidification by the renal tubules (renal tubular acidosis), or in early renal failure when acid excretion is impaired. Hospital-acquired hyperchloremic acidosis is usually caused by the infusion of large volumes of normal saline (0.9%). Hyperchloremic acidosis should lead to increased renal excretion of ammonium, and measurement of urinary ammonium can therefore be used to differentiate between renal and extrarenal causes of normal anion-gap acidosis. However, since urinary ammonium is seldom measured, the urinary anion gap and urinary osmolal gap are often used as surrogate measures of excretion of urinary ammonium. The urine anion gap ([Na+] + [K+] – Cl]) is usually negative in normal anion-gap acidosis, but it will become positive when excretion of urinary ammonium (NH4+) (as ammonium chloride [NH4Cl]) is impaired, as in renal failure, distal renal tubular acidosis, or hypoaldosteronism.
What is a useful approach to the analysis and treatment of a metabolic alkalosis?
The normal kidney is highly efficient at excreting large amounts of bicarbonate, and accordingly, the generation of metabolic alkalosis requires both an increase in alkali and impairment in renal excretion of bicarbonate. Gastric fluid loss and diuretic use account for the majority of metabolic alkalosis cases. By measuring chloride in urine, one can distinguish between chloride-responsive and chloride-resistant metabolic alkalosis. If the kidneys perceive a reduced “effective circulating volume,” they avidly reabsorb filtered sodium, bicarbonate, and chloride, largely through activation of the renin–angiotensin–aldosterone system, thus reducing the concentration of urinary chloride. A (spot sample) urinary chloride concentration of less than 25 mmol per liter is reflective of chloride-responsive metabolic alkalosis. Administration of fluids with sodium chloride (usually with potassium chloride) restores effective arterial volume, replenishes potassium ions, or both with correction of metabolic alkalosis. Metabolic alkalosis with a urinary chloride concentration of more than 40 mmol per liter is mainly caused by inappropriate renal excretion of sodium chloride, often reflecting mineralocorticoid excess or severe hypokalemia (potassium concentration <2 mmol per liter). The administration of sodium chloride does not correct this type of metabolic alkalosis, which, for that reason, is called “chloride-resistant.” Diuretic-induced metabolic alkalosis is an exception because the concentration of chloride in urine may increase initially, until the diuretic effect wanes, after which the concentration of chloride in the urine will fall below 25 mmol per liter.
How is the “delta anion gap” helpful in the evaluation of mixed metabolic acid–base disorders?

In high anion-gap metabolic acidosis, the magnitude of the anion gap increase (delta AG, or ΔAG) is related to the decrease in the bicarbonate ions (Δ[HCO3]). To diagnose a high anion-gap acidosis with concomitant metabolic alkalosis or normal anion-gap acidosis, the so-called delta-delta (Δ-Δ) may be used. The delta gap is the comparison between the increase (delta) in the anion gap above the upper reference value (e.g., 12 mmol per liter) and the change (delta) in the concentration of bicarbonate ions from the lower reference value of bicarbonate ions (e.g., 24 mmol per liter). In ketoacidosis, there is a 1:1 correlation between the rise in anion-gap and the fall in concentration of bicarbonate. In lactic acidosis, the decrease in concentration of bicarbonate is 0.6 times the increase in anion gap (e.g., if the anion gap raises 10 mmol per liter, the concentration of bicarbonate should decrease about 6.0 mmol per liter). This difference is probably due to the lower renal clearance of lactate compared with keto-anions. Hydrogen buffering in cells and bone takes time to reach completion. Accordingly, the ratio may be close to 1:1 with “very acute” lactic acidosis (as with seizures or exercise to exhaustion). If the ΔAG – Δ[HCO3] in ketoacidosis or if 0.6 ΔAG – Δ[HCO3] in lactic acidosis = 0±5 mmol per liter, simple anion-gap metabolic acidosis is present. A difference greater than 5 mmol per liter suggests a concomitant metabolic alkalosis, and if the difference is less than –5 mmol per liter, a concomitant normal anion-gap metabolic acidosis is diagnosed.

Thursday, September 25, 2014

2014 AMA/ACC guidelines for the NSTE-ACS

This is a super short summary of the guidelines published on-line a couple of days ago. It basically contains what we need to know in the ED to treat these patients. There are dozens of pages on what to do after the patient leaves the department. If you are interested in that, go ahead and download the free PDF and get cozy with it. Here is the link:

You will notice that the guidelines are very similar to prior the prior edition. There are only few changes with regards with anti platelet agent choices, the elimination of CK-MB as diagnostic test, oxygen is only for those with hypoxia and a more liberal approach to coronary imaging and interventions.

OK.. now to the super condensed summary.

Class I
1. ECG within 10 mins or arrival.
2. Repeat ECG q 15-20 mins in patient who remain symptomatic and initial EKG was non-diagnostic.
3. Serial cardiac troponin I or T levels at presentation and 3 to 6 hours after symptom onset
4. Additional troponin levels should be obtained beyond 6 hours after symptom onset in patients with normal troponin levels on serial examination when changes on ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS
5. Risk scores (like GRACE score) should be used to assess prognosis in patients with NSTE-ACS
Class IIa
1. Risk-stratification models can be useful in management (like TIMI).
2. Get ECG leads V7 to V9 in patients whose 
initial ECG is nondiagnostic and who are at intermediate/high risk of ACS looking for posterior MI.
Class IIb
1. Continuous monitoring with 12-lead ECG
2. Measurement of B-type natriuretic peptide or N-terminal pro–B-type natriuretic peptide may be considered to assess risk in patients with suspected ACS

Biomarkers: Diagnosis
Class I
1. If the time of symptom onset is ambiguous, the time of presentation should be considered the time of onset for assessing troponin values
Class III: No Benefit

1. If you have troponins in your lab, forget about creatine kinase myocardial isoenzyme (CK-MB) and myoglobin are not useful for diagnosis of ACS

Biomarkers: Prognosis
Class I

1. The presence and magnitude of troponin elevations are useful for short- and long-term prognosis

Discharge from the ED
Class IIa
1. OK to admit at risk patients to chest pain units for repeat ECG's an trops at 3- to 6-hour intervals
2. Patients with normal serial ECGs and cardiac troponins can have a treadmill ECG, stress myocardial perfusion imaging, or stress echocardiography before discharge or within 72 hours after discharge.
3. Reasonable alternatives are coronary computed tomography angiography to assess coronary artery anatomy or rest myocardial perfusion imaging with a technetium-99m radiopharmaceutical to exclude myocardial ischemia.
4. Those who go home, get daily aspirin, short-acting nitroglycerin, and other medication if appropriate (e.g., beta blockers), with instructions about activity level and clinician follow-up.

Early Hospital Care
Class I

1. Supplemental oxygen should be administered to patients with NSTE-ACS with arterial oxygen saturation less than 90%, respiratory distress, or other high-risk features of hypoxemia.
Class I
1. Patients with NSTE-ACS with continuing ischemic pain should receive sublingual nitroglycerin 
(0.3 mg–0.4 mg) every 5 minutes for up to 3 doses, after which an assessment should be made about the need for intravenous nitroglycerin if not contraindicated
2. Intravenous nitroglycerin is indicated for patients with NSTE-ACS for the treatment of persistent ischemia, heart failure (HF), or hypertension.
Analgesic Therapy
Class IIb

1. If no contrainfications, Morphine for non-controlled ischemic pain is just fine.
Class III:

1. Don’t use NSAID’s and if they are taking NSAID’s for other reasons, stop it.
Beta-Adrenergic Blockers
Class I
1. Oral beta-blocker therapy should be initiated within the first 24 hours in patients who do not have any of the following: 1) signs of HF, 2) evidence of low-output state, 3) increased risk for cardiogenic shock, or 4) other contraindications to beta blockade (e.g., PR interval >0.24 second, second- or third-degree heart block without a cardiac pacemaker, active asthma, or reactive airway disease)
2. In patients with concomitant NSTE-ACS, stabilized HF, and reduced systolic function, it is recommended to continue beta-blocker therapy with 1 of the 3 drugs proven to reduce mortality in patients with HF: sustained-release metoprolol succinate, carvedilol, or bisoprolol.
3. Patients with documented contraindications to beta blockers in the first 24 hours of NSTE-ACS should be reevaluated to determine their subsequent eligibility. 

1. It is reasonable to continue beta-blocker therapy in patients with normal left ventricular (LV) function with NSTE-ACS 
III: Harm
1. Administration of intravenous beta blockers is potentially harmful in patients with NSTE-ACS who have risk factors for shock (poor EF, tachycardic, know myocardiopathy)
Calcium Channel Blockers
Class I
1. In patients with NSTE-ACS, continuing or frequently recurring ischemia, and a contraindication to beta blockers, a nondihydropyridine calcium channel blocker (CCB) (e.g., verapamil or diltiazem) should be given as initial therapy in the absence of clinically significant LV dysfunction, increased risk for cardiogenic shock, PR interval greater than 0.24 second, or second- or third- degree atrioventricular block without a cardiac pacemaker
2. CCBs are recommended for ischemic symptoms when beta blockers are not successful, are contraindicated, or cause unacceptable side effects. 
Class III: Harm

1. Immediate-release nifedipine should not be administered to patients with NSTE-ACS in the absence of beta-blocker therapy
Antiplatelet Agents
Class I
1. If non-allergic, give Aspirin to everyone (162 mg to 325 mg) as soon as possible after presentation, and a maintenance dose of aspirin (81 mg/d to 162 mg/d) should be continued indefinitely
2. If Aspirin allergic, give clopidogrel followed by a daily maintenance dose should be administered
Class IIa

1. It is reasonable to use ticagrelor in preference to clopidogrel in patients with NSTE ACS who undergo an early invasive or ischemia-guided strategy.
Class IIb

1. In patients with NSTE-ACS treated with an early invasive strategy and dual anti platelet therap  (DAPT) with intermediate/high-risk features (e.g., positive troponin), a glycoprotein (GP) IIb/IIIa inhibitor may be considered as part of initial antiplatelet therapy. Preferred options are eptifibatide or tirofiban.


Class I
1. In patients with NSTE-ACS, anticoagulation, in addition to antiplatelet therapy, is recommended for all patients irrespective of initial treatment strategy. Treatment options include:
- Enoxaparin: 1 mg/kg subcutaneous (SC) every 12 hours (reduce dose to 1 mg/kg SC once daily in patients with creatinine clearance [CrCl] <30 mL/min), continued for the duration of hospitalization or until percutaneous coronary intervention (PCI) is performed. An initial intravenous loading dose is 30 mg

- Bivalirudin: 0.10 mg/kg loading dose followed by 0.25 mg/kg per hour (only in patients managed with an early invasive strategy), continued until diagnostic angiography or PCI, with only provisional use of GP IIb/IIIa inhibitor, provided the patient is also treated with DAPT

- Fondaparinux: 2.5 mg SC daily, continued for the duration of hospitalization or until PCI is performed

- If PCI is performed while the patient is on fondaparinux, an additional anticoagulant with anti-IIa activity (either UFH or bivalirudin) should be administered because of the risk of catheter thrombosis

- UFH IV: initial loading dose of 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg per hour (maximum 1,000 IU/h) adjusted per activated partial thromboplastin time to maintain therapeutic anticoagulation according to the specific hospital protocol, continued for 48 hours or until PCI is performed

Class III: Harm

1. In patients with NSTE-ACS (i.e., without ST elevation, true posterior MI, or left bundle-branch block not known to be old), intravenous fibrinolytic therapy should not be used.
Ischemia-Guided Strategy Versus Early Invasive Strategies

Early Invasive and Ischemia-Guided Strategies
Class I
1. An urgent/immediate invasive strategy (diagnostic angiography with intent to perform revascularization if appropriate based on coronary anatomy) is indicated in patients (men and women) with NSTE-ACS who have refractory angina or hemodynamic or electrical instability (without serious comorbidities or contraindications to such procedures).
2. An early invasive strategy (diagnostic angiography with intent to perform revascularization if appropriate based on coronary anatomy) is indicated in initially stabilized patients with NSTE- ACS (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events
Class IIa

1. It is reasonable to choose an early invasive strategy (within 24 hours of admission) over a delayed invasive strategy (within 24 to 72 hours) for initially stabilized high-risk patients with NSTE-ACS. For those not at high/intermediate risk, a delayed invasive approach is reasonable

1. In initially stabilized patients, an ischemia-guided strategy may be considered for patients with NSTE ACS (without serious comorbidities or contraindications to this approach) who have an elevated risk for clinical events  
2. The decision to implement an ischemia-guided strategy in initially stabilized patients (without serious comorbidities or contraindications to this approach) may be reasonable after considering clinician and patient preference.
III: No Benefit

1. An early invasive strategy (i.e., diagnostic angiography with intent to perform revascularization) is not recommended in patients with:
- Extensive comorbidities (e.g., hepatic, renal, pulmonary failure, cancer), in whom the risks of revascularization and comorbid conditions are likely to outweigh the benefits of revascularization.  
- Acute chest pain and a low likelihood of ACS who are troponin- negative, especially women.

Ufff. That was painful !  But not as painful as the 71 pages of the whole document. Now go and tell your friends that NSTE-ACS has new guidelines with just a few changes.

Thursday, July 31, 2014

Scorpion Envenomation. Not so bad, but when it bad... is BAD!

Still is summer time and in some parts of the world, scorpions are a threat. There are dozens of varieties to chose from. Here are some basics about the patophysiology of Scorpion Envenomation. From this week's NEJM.

What are the general characteristics of scorpion stings?
Most scorpion stings cause localized pain, whereas only an estimated 10% of stings, even from the most dangerous scorpions, result in severe systemic envenomation. Edema, erythema, paresthesias, muscle fasciculations, and numbness may occur at the site of the sting. It is often difficult to see the sting site or to identify inflammation at the site, despite substantial local pain. Most cases of severe envenomation occur in children. Systemic envenomation is characterized by neuromuscular abnormalities resulting from effects on the somatic and cranial nerves, both cholinergic and adrenergic excitation of the autonomic nervous system, pulmonary edema, and cardiac effects.
What are the autonomic effects of scorpion stings?
Excitation of the autonomic nervous system is characterized by both parasympathetic and sympathetic responses. Parasympathetic, cholinergic effects may include hypersalivation, profuse diaphoresis, lacrimation, miosis, diarrhea, vomiting, bradycardia, hypotension, increased respiratory secretions, and priapism. Sympathetic, adrenergic effects include tachycardia, hypertension, mydriasis, hyperthermia, hyperglycemia, agitation, and restlessness. Whereas most parasympathetic effects tend to occur early, sympathetic effects persist because of the release of catecholamines and are responsible for severe envenomation.
What are possible cardiovascular complications of scorpion envenomation? A range of cardiac conduction abnormalities occur in about one third to one half of patients with systemic envenomation. These effects include atrial tachycardia, ventricular extrasystoles, T-wave inversion, ST-T wave changes, and, less frequently, bundle-branch block. Increased autonomic stimulation caused by increased vagal effects on the heart and sympathetic stimulation are the probable causes of these effects. Hypertension is common and occurs early in response to sympathetic stimulation. Hypotension is less common, occurs with the development of severe envenomation, and often requires intervention with vasopressors and fluid resuscitation. Many factors are at play in the development of hypotension, with cholinergic stimulation causing vasodilation, fluid loss, and myocardial depression. Cardiac dysfunction resulting from catecholamine-induced myocarditis and myocardial ischemia complicates severe envenomation from androctonus, buthus, mesobuthus, and tityus scorpions. This complication may result in pulmonary edema and cardiogenic shock.

What are the principles of treatment for cases of severe scorpion envenomation? The specific treatment is the administration of antivenom combined with symptomatic and supportive treatment, including prazosin and dobutamine in patients with cardiovascular toxic effects and benzodiazepines when there is neuromuscular involvement. Symptoms related to the site of the sting should be managed with appropriate analgesia with acetaminophen and antiinflammatory agents, depending on severity. Once severe envenomation has developed, the administration of antivenom may be less effective, since its primary therapeutic action is to bind toxins; it does not reverse established pathophysiological injury, such as excess levels of catecholamine, pulmonary edema, and cardiogenic shock.
- Scorpion envenomation are rarely fatal, but children are at high risk.
- For most, supportive treatment is fine if no signs of nervous or cardiac system involvement. 
- If is going to be bad, it goes from bad to worse very quickly. Therefore, if antivenom is available, give it early and transfer sooner rather than later.
- Prazosin, an alfa blocker, and dobutamine in combination for patients with cardiovascular symptoms. And benzos for neuromuscular involvement.
- Not all scorpions are scary, some can also be cute... like this one!

Monday, April 14, 2014

Hypersensitivity to Hymenoptera Sting... Not a Little Problem !

Spring is here and with that, the return of the hymenoptera stings coming to the ER. So we are going to review this week's NEJM article on the topic using the question and answer format.

What is the antigenic cross-reactivity between Hymenoptera species?
The Hymenoptera insects whose stings cause allergy are generally from three families: Apidae (honeybees and bumblebees), Vespidae (hornets, wasps, and yellow jackets), and Formicidae (fire ants). The molecular characteristics of the venoms from the three families of Hymenoptera are sufficiently different that there is very little antigenic cross-reactivity. Within families (e.g., vespids), there can be substantial cross-reactivity among the allergens present in the venoms; however, honeybee and bumblebee allergies are distinct.

What is the pathophysiology of an allergic reaction to a hymenoptera sting, and how common is an anaphylactic reaction?
In sensitized persons, a sting can cause the injected venom to bind to venom-specific IgE on mast cells, cross-linking high-affinity IgE receptors and subsequently leading to the rapid release of mast-cell mediators, including histamine, leukotrienes, prostaglandins, and platelet-activating factor. The released mast-cell mediators can cause a spectrum of allergic reactions, from local reactions (affecting small or large [≥10 cm] areas) or urticaria to anaphylaxis and even death. Patients with large local reactions usually do not have a systemic reaction to subsequent stings (with systemic reactions occurring in <10% of these patients), nor do children with isolated urticaria. However, a previous systemic reaction in a patient with venom-specific IgE is associated with a high risk of subsequent systemic reaction, which may occur in 30 to 60% of these patients. Anaphylaxis due to a hymenoptera sting causes at least 40 deaths per year in the United States, although this number is probably an underestimate. Severe systemic allergic reactions occur in approximately 0.4 to 0.8% of children and 3.0% of adults.

What are the risk factors for a severe reaction to a hymenoptera sting and how should it be treated?
Acute systemic reactions typically occur very rapidly after a hymenoptera sting but may be delayed for several hours or be biphasic. The factors associated with an increased risk of severe reaction include being stung by a honeybee (greater risk than with other hymenoptera), underlying mast-cell disorders with elevated serum-tryptase levels at baseline, a previous severe reaction, preexisting cardiovascular disease, and concomitant treatment with a beta-blocker, angiotensin-converting–enzyme inhibitor, or both. Anaphylaxis can present with a spectrum of signs and symptoms affecting multiple organ systems, including the skin, gastrointestinal tract, cardiovascular system, nervous system, and both the upper and lower respiratory tracts; hallmarks of anaphylaxis are the development of hypotension or the involvement of more than one organ system. The treatment of anaphylaxis in the emergency department should include epinephrine for any patient who has more than cutaneous symptoms; epinephrine should also be considered in adults with urticaria alone. H1-antihistamines can help relieve cutaneous signs and symptoms. For respiratory symptoms, supplemental oxygen and inhaled beta2-agonists should be used. For patients with hypotension, volume resuscitation is indicated, with 1 to 2 liters of 0.9% (isotonic) saline infused rapidly (e.g., a dose of 5 to 10 ml per kilogram in the first 5 to 10 minutes in an adult, and 10 ml per kilogram in a child).

Who should receive venom immunotherapy?
Subcutaneous immunotherapy should be considered in all patients who have had a systemic allergic reaction to an insect sting and who have a positive skin test or a positive result on an in vitro test for venom-specific IgE antibodies. Children 16 years of age or younger who have had isolated cutaneous systemic reactions to insect stings have a very low risk of subsequent reactions and do not require venom immunotherapy. Venom immunotherapy is also generally not necessary in patients who have had only a large local reaction, because their risk of subsequent systemic reactions is relatively low. However, patients with unavoidable or frequent exposures (e.g., beekeepers) may benefit, because observational data indicate that, after immunotherapy, local reactions are reduced in size and duration.

Key points to remember:
- Hymenoptera stings CAN kill, so take them seriously, specially those with prior severe reactions and honeybee stings.
- It is an IgE hypersensitivity reaction, therefore it is fast in most cases, but don't forget it can be biphasic.
- High risk are patients on beta blockers, ACEI and cardiovascular disease, the very young and old.
- Anaphylaxis is hypotension plus one other system involved: Skin, GI, respiratory or neurologic. Don't miss it !
- If it looks bad... IS bad. Get epinephrine IM mas rapido and quickly start an epinephrine drip and ensure good volume resuscitation. Antihistaminics, steroids and beta agonist are secondary agents.
- Arrange for follow up in all severe cases for possible immunotherapy, let the PCP and allergist make that call.
- Don't forget your dog... consult the vet right away! '',