Saturday, December 13, 2014

Lactic Acidosis... is it really that bad? Oh yeah. It is bad!

Lactic acid is often associated with badness, and the higher the number the worse the patient is. However, producing lactate is an appropriate stress response, and when it accumulates due to poor utilization, it indicates serious cellular function problems.  This next diagram shows the multiple causes on lactic acidosis.

Hyperlactatemia occurs when lactate production exceeds lactate consumption. In tissue hypoxia, whether global or localized, lactate is overproduced and underutilized as a result of impaired mitochondrial oxidation. Even if systemic oxygen delivery is not low enough to cause generalized hypoxia, microcirculatory dysfunction can cause regional tissue hypoxia and hyperlactatemia. Hyperlactatemia can also result from aerobic glycolysis, a term denoting stimulated glycolysis that depends on factors other than tissue hypoxia. Activated in response to stress, aerobic glycolysis is an effective, albeit inefficient, mechanism for rapid generation of ATP. In the hyperdynamic stage of sepsis, epinephrine-dependent stimulation of the β2-adrenoceptor augments the glycolytic flux both directly and through enhancement of the sarcolemmal Na+,K+-ATPase (which consumes large quantities of ATP). Other disorders associated with elevated epinephrine levels, such as severe asthma (especially with overuse of β2-adrenergic agonists), extensive trauma, cardiogenic or hemorrhagic shock, and pheochromocytoma, can cause hyperlactatemia through this mechanism. Drugs that impair oxidative phosphorylation, such as antiretroviral agents and propofol, can augment lactic acid production and on rare occasions cause severe lactic acidosis. Cardiogenic or hypovolemic shock, severe heart failure, severe trauma, and sepsis are the most common causes of lactic acidosis, accounting for the vast majority of cases.

An elevated serum anion gap, particularly a value higher than 30 mmol per liter, can provide supportive evidence. However, other causes of a raised anion gap, such as ketoacidosis and toxic alcohol ingestion, should always be considered. A normal anion gap does not rule out lactic acidosis. In one study, 50% of patients with a serum lactate level of 5 to 10 mmol per liter did not have an elevated anion gap. Correction of the anion gap for the effect of serum albumin can improve its sensitivity, but many cases will still escape detection. Therefore, the serum anion gap lacks sufficient sensitivity or specificity to serve as a screening tool for lactic acidosis. An elevated blood lactate level is essential for confirmation of the diagnosis. Previously, the definition of lactic acidosis included a blood pH of 7.35 and a serum [HCO3] of 20 mmol per liter or lower. However, the absence of one or both of these features because of coexisting acid–base disorders does not rule out lactic acidosis.


When treating patient with Lactic Acidosis, restoring tissue perfusion after hemodynamic compromise is essential in the treatment of patients with lactic acidosis. Vasopressors and inotropic agents should be administered as needed. Crystalloid and colloid solutions are both effective in restoring tissue perfusion in patients with sepsis or hypovolemia. Red-cell transfusions should be administered to maintain the hemoglobin concentration at a level above 7 g per deciliter. An adequate PO2 should be maintained by ensuring an appropriate inspired oxygen concentration, with endotracheal intubation and mechanical ventilation as needed. Given the potentially deleterious effects of an acidic environment, some clinicians recommend therapy with intravenous sodium bicarbonate for severe acidemia (blood pH, <7.2). However, the value of bicarbonate therapy in reducing mortality or improving hemodynamics remains unproven. Using dialysis to provide bicarbonate can prevent a decrease in ionized calcium, prevent volume overload and hyperosmolality (potential complications of bicarbonate infusion), and remove substances associated with lactic acidosis, such as metformin. Resuscitative efforts should be complemented by measures targeting the cause or causes of lactic acidosis.


Measurement of the blood lactate level remains the cornerstone of monitoring for lactic acidosis. Lactate can be measured in arterial or venous blood, since the values are virtually interchangeable. An interval of 2 to 6 hours has been suggested for repeat lactate measurements, but this issue has not been examined rigorously. Changes in levels of blood lactate have been used to guide therapy. In a randomized, controlled study, a reduction of at least 20% in serum lactate levels every 2 hours was targeted for the first 8 hours of resuscitation; achievement of this target of lactate clearance was associated with decreased morbidity and mortality. Evidence that in seriously ill patients even lactate levels at the upper end of the normal range are associated with poor clinical outcomes argues for the normalization of blood lactate as a primary goal of therapy



In summary:

- Lactic acid = Cellular dysfunction, and the higher the number, the sicker the patient is.
- Normal Anion Gap does not rule out lactic acidosis, nor does HCO3 or pH levels. Measured lactic acid is the best way to diagnose.
- When treating, focus on tissue perfusion first. Volume expansion, oxygenation (including mechanical ventilation), blood transfusion (if Hg < 7), bicarbonate infusions (maybe!), and dialysis are all appropriate in certain clinical scenarios.
 Lactate clearance of 10% per hour of treatment is a good treatment goal.



Friday, November 28, 2014

Some important data about AAA...

OK... we are going to talk AAA, and this is not the American Alcoholic Anonymous! Abdominal Aortic Aneurysms kill, and kill fast when not diagnosed promptly. Here are some useful tips about this deadly condition so it will easy for you to recognized it.



Nonmodifiable risk factors for abdominal aortic aneurysm include older age, male sex, and a family history of the disorder. Starting at 50 years of age for men and 60 to 70 years of age for women, the incidence of aneurysms increases significantly with each decade. The risk of abdominal aortic aneurysm is approximately four times as high among men as among women and four times as high among people with a family history of the disorder as among those without a family history. Smoking is the strongest modifiable risk factor. Other, less prominent risk factors for abdominal aortic aneurysm include hypertension, an elevated cholesterol level, obesity, and preexisting atherosclerotic occlusive disease.

What are the recommendations for screening for abdominal aortic aneurysms?
Ultrasonography is the primary method used for screening and is highly sensitive (95%) and specific (100%). CT scanning and magnetic resonance imaging (MRI) are expensive, incur risks (radiation exposure from CT and risks associated with intravenous contrast material), and should not be used for screening but rather reserved for preinterventional planning. The current recommendations of the U. S. Preventive Services Task Force are a one-time screening in men 65 to 75 years of age who have ever smoked (grade B recommendation) and selective screening in men 65 to 75 years of age who have never smoked (grade C recommendation). Medicare also covers screening for patients with a family history of abdominal aortic aneurysm. Data from nonrandomized studies suggest that there may be subgroups of women who benefit from screening; however, this finding has not been prospectively validated.


What are the indications for surgical repair of an abdominal aortic aneurysm?
Under most circumstances, aneurysms should not be prophylactically repaired unless they are at least 5.5 cm in diameter. Nevertheless, there are occasions when repair of small aneurysms should be considered. Symptomatic aneurysms should be immediately repaired. Pain in the abdomen, back, or flank is the most common symptom, but aneurysms can produce many other symptoms or signs (e.g., hematuria or gastrointestinal hemorrhage). The rate of growth is another important predictor of rupture; aneurysms that expand by more than 0.5 cm in diameter over a period of 6 months should be considered for repair regardless of the absolute size. The observations that aneurysms rupture at a smaller size in women than in men and that women have higher rupture-related mortality than men have led some experts to recommend a diameter of 5.0 cm as the threshold for elective intervention in women. Other factors that are associated with an increased risk of rupture and may prompt repair at a threshold of less than 5.5 cm include the presence of a saccular aneurysm (most aneurysms are fusiform) and a family history of abdominal aortic aneurysm.


What surgical techniques are available for repair of an abdominal aortic aneurysm?

Two approaches to repairing aneurysms are currently available: open repair (performed since the 1950s) and endovascular repair (first performed in 1987). Endovascular repair, a less invasive approach, involves the intraluminal introduction of a covered stent through the femoral and iliac arteries; the stent functions as a sleeve that passes through the aneurysm sac, anchoring in the normal aorta above the aneurysm and in the iliac arteries below the aneurysm. To be eligible for endovascular repair, a patient must have appropriate anatomy, including iliac vessels that are of sufficient size to allow introduction of the graft and an aortic neck above the aneurysm that allows the proximal graft to be anchored without covering the renal arteries. Thus, with existing techniques, there are some infrarenal aneurysms that are not amenable to endovascular repair. The use of endovascular repair has grown steadily in the United States, and this procedure is currently performed in more than 75% of patients undergoing surgical intervention for abdominal aortic aneurysm, with a portion of the remaining patients having unsuitable anatomy. Endovascular repair confers an initial survival benefit; however, this benefit disappears over a period of 1 to 3 years. Endovascular repair and open repair are associated with similar mortality over the long term (8 to 10 years).


Thursday, November 6, 2014

Malaria - Quick review

Although Ebola has been all the furor in the recent weeks, fever in travelers is NOT Ebola most of the times. Depending on the region and season, the usual culprits are more likely than Ebola, these include malaria, dengue, yellow fever, chikungunia virus, hepatitis, salmonella and other intestinal bugs, multiple parasites among others. Here is the Q&A for malaria and babesia from this month's NEJM.

  
What is the annual incidence of malaria in the United States?
In the United States, the annual incidence of malaria is approximately 1500 cases. In 2010, a total of 1691 cases were reported to the Centers for Disease Control and Prevention (CDC), the largest number reported since 1980; P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 58%, 19%, 2%, and 2% of cases, respectively.

How do malaria and babesiosis differ in appearance on a peripheral blood smear?
Intraerythrocytic parasites are seen in both malaria and babesiosis. Plasmodia metabolize heme to form an intracellular crystallized pigment, hemozoin. Although hemozoin is not invariably identified in cases of malaria, its presence reliably distinguishes malaria infection from babesia infection. Malaria parasites can be distinguished from B. [Babesia] microti by the presence of recognizable gametocytes (characteristically banana-shaped in Plasmodium falciparum and round, with a granular appearance, in nonfalciparum species). In addition, intracellular vacuoles and extracellular merozoites are unusual in malaria but common in babesiosis, and the classic “Maltese cross” (a tetrad of parasites budding at right angles) is unique to babesia species.

Which malaria species can remain dormant in the liver?
In the case of P. vivax and P. ovale, some sporozoites (immature malaria parasites) do not replicate immediately when they invade hepatocytes but remain dormant (as hypnozoites) for prolonged periods. The average time to relapse is approximately 9 months, but it can range from weeks to years. The interval to relapse depends on the strain (earlier with tropical strains and later with temperate strains), the initial inoculum, and host factors (e.g., febrile illnesses can trigger relapse associated with P. vivax). None of the commonly used prophylactic agents (chloroquine, mefloquine, doxycycline, or atovaquone–proguanil) eliminate hypnozoites. Primaquine, the only effective drug against dormant hypnozoites, has not been approved by the Food and Drug Administration for primary prophylaxis, but the CDC endorses its use for prophylaxis in Latin American countries where P. vivax predominates, because the drug can prevent both primary attacks and relapses caused by all species that are a source of malarial infection.

How is acute or recurrent P. vivax infection treated?
In patients with acute or recurrent malaria infection, treatment depends on the species and the resistance status in the area where the infection was acquired. P. falciparum is resistant to chloroquine in most regions in which it is endemic and resistant to mefloquine in parts of Southeast Asia. In contrast, nonfalciparum malaria parasites do not have substantial resistance to mefloquine, and the distribution of chloroquine-resistant P. vivax malaria is limited, occurring primarily in Indonesia and Papua New Guinea. After treatment is initiated, peripheral-blood smears should be obtained daily for 4 days (parasitemia is typically eliminated by day 4), on days 7 and 28 to confirm eradication, and at any time symptoms recur, suggesting treatment failure. In areas other than those with known chloroquine resistance, chloroquine, followed by a 14-day course of primaquine to prevent subsequent relapses, remains the standard treatment for P. vivax parasitemia. Given the risk of hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency who receive treatment with primaquine, potential recipients should be tested for G6PD deficiency. Among patients with a contraindication to primaquine therapy, treatment with chloroquine alone carries a 20% risk of relapse; extended chloroquine prophylaxis can be offered to patients who have frequent relapses.




Thursday, October 23, 2014

Community Acquired Pneumonia - Keep it simple, but not too simple.

One of the oldest (and deadliest) diseases in history, pneumonia continues being a threat. Recognizing and treating properly are the best way to minimize complications. Another good review from this week's NEJM.




What are the most common causes of CAP? Although pneumococcus remains the most commonly identified cause of CAP, the frequency with which it is implicated has declined, and it is now detected in only about 10 to 15% of inpatient cases in the United States. Other bacteria that cause CAP include Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Pseudomonas aeruginosa, and other gram-negative bacilli. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for CAP caused by H. influenzae and Mor. catarrhalis. P. aeruginosa and other gram-negative bacilli also cause CAP in persons who have COPD or bronchiectasis, especially in those taking glucocorticoids. There is a wide variation in the reported incidence of CAP caused by Mycoplasma pneumoniae and Chlamydophila pneumoniae (so-called atypical bacterial causes of CAP), depending in part on the diagnostic techniques that are used. During influenza outbreaks, the circulating influenza virus becomes the principal cause of CAP that is serious enough to require hospitalization, with secondary bacterial infection as a major contributor.

What evaluation do the authors recommend to determine the cause of community-acquired pneumonia in a hospitalized patient? In hospitalized patients with CAP, the authors favor obtaining Gram’s staining and culture of sputum, blood cultures, testing for legionella and pneumococcal urinary antigens, and multiplex PCR assays for Myc. pneumoniae, Chl. pneumoniae, and respiratory viruses, as well as other testing as indicated in patients with specific risk factors or exposures. A low serum procalcitonin concentration (<0.1 µg per liter) can help to support a decision to withhold or discontinue antibiotics. Results on Gram’s staining and culture of sputum are positive in more than 80% of cases of pneumococcal pneumonia when a good-quality specimen (>10 inflammatory cells per epithelial cell) can be obtained before, or within 6 to 12 hours after, the initiation of antibiotics. Blood cultures are positive in about 20 to 25% of inpatients with pneumococcal pneumonia but in fewer cases of pneumonia caused by H. influenzae or P. aeruginosa and only rarely in cases caused by Mor. catarrhalis.

What are the guidelines for treating community-acquired pneumonia in outpatients and inpatients? For outpatients without coexisting illnesses or recent use of antimicrobial agents, IDSA/ATS [Infectious Diseases Society of America and the American Thoracic Society] guidelines recommend the administration of a macrolide (provided that <25% of pneumococci in the community have high-level macrolide resistance) or doxycycline. For outpatients with coexisting illnesses or recent use of antimicrobial agents, the guidelines recommend the use of levofloxacin or moxifloxacin alone or a beta-lactam (e.g., amoxicillin–clavulanate) plus a macrolide. The authors argue, however, that a beta-lactam may be favored as empirical therapy for CAP in outpatients, since most clinicians do not know the level of pneumococcal resistance in their communities, and Str. pneumoniae is more susceptible to penicillins than to macrolides or doxycycline. Even though the prevalence of Str. pneumoniae as a cause of CAP has decreased, they raise concern about treating a patient with a macrolide or doxycycline to which 15 to 30% of strains of Str. pneumoniae are resistant. For patients with CAP who require hospitalization and in whom no cause of infection is immediately apparent, IDSA/ATS guidelines recommend empirical therapy with either a beta-lactam plus a macrolide or a quinolone alone.

What is the appropriate duration of antibiotic therapy for community-acquired pneumonia? Early in the antibiotic era, pneumonia was treated for about 5 days; the standard duration of treatment later evolved to 5 to 7 days. A meta-analysis of studies comparing treatment durations of 7 days or less with durations of 8 days or more showed no differences in outcomes, and prospective studies have shown that 5 days of therapy are as effective as 10 days and 3 days are as effective as 8. Nevertheless, practitioners have gradually increased the duration of treatment for CAP to 10 to 14 days. The authors argue that a responsible approach to balancing antibiotic stewardship with concern about insufficient antibiotic therapy would be to limit treatment to 5 to 7 days, especially in outpatients or in inpatients who have a prompt response to therapy. Pneumonia that is caused by Staph. aureus or gram-negative bacilli tends to be destructive, and concern that small abscesses may be present has led clinicians to use more prolonged therapy, depending on the presence or absence of coexisting illnesses and the response to therapy.

Summary
- Strep pneumo still is the most common bug, and is more sensitive to penicillins than macrolides or doxy.
- Uncomplicated, outpatient treatment: Macrolide or Doxy, consider adding a beta-lactam if high risk; alternatively, respiratory quinolone by it self.
- Sputum gram stain and cultures.. maybe, don't expect to get too much from them.
- 5 days of treatment is as good as 10.






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.