Month: October 2014

My own opinion about the past, the present, and the future of Clinical Pharmacy in China

October 26, 2014 Pharmacy Schools No comments , , ,

Clinical Pharmacy is a new term with a history of less than a century. One of which the ancestor is the UCSF School of Pharmacy, United States, who started the clinical pharmacy after 1960, with the landscape of “The UCSF Ninth Floor Project”.

Despite that Pharmacy Schools in China had started the discipline of Clinical Pharmacy since nearly 35 years, this area of pharmacy stays in the primary role of Biopharmaceutics, GLP, Pharmacy Analysis, where there is still a long distance to the clinical pharmacy practice – providing direct daily clinical services to our patients, to our colleagues, and other healthcare professionals.

Pharmacy dreamers and doers had tried hard to make this discipline more and more necessary, and meaningful. For example, the West China School of Pharmacy had created the first degree of clinical pharmacy, the bachelor degree of clinical pharmacy, in 1980. The most recent and inspiring event in the history of clinical pharmacy in China was the launch of the post-graduate program Clinical Pharmacy Residency, begun in 2006 in West China Hospital. It’s really a milestone, which symboling the dire and the attempts of these pharmacy dreamers and doers to transfer the formal clinical pharmacy into the new healthcare provider role.

However, in most of hospitals in China, not limited to ones in the past but I could say including ones today, the healthcare pharmacists’ role remains a far away from the clinical service provider. Even in the university hospital such as West China Hospital, the pharmacists there are still in confusion about the professional responsibility of pharmacists in healthcare system, or most of they would ask what should I do when I am there? Or what is my obligation. They do not lack passion, they do not lack diligence, so what is the issue? Thus I made some brief summary about the difficulty we face at present.

First, the social rank of healthcare pharmacists in China is relative low compared with other healthcare professionals like physicians, surgeons, etc. This is not due to that pharmacists have fewer knowledge learnt from school, nor we have less college education background. This is due to what services we can provide to our patients, our colleagues, and other healthcare professionals and the society. No need, no value. Think, why a physician should go for a pharmacist who cannot tell him/her how to figure the complex pharmacotherapy problem out?

Second, we have not had this profession yet. Is there any national standard which defines the concepts, the criterias and requirements, the privileges, and the obligations of clinical pharmacists? There are many young trying to become a clinical pharmacist. There are many older pharmacists dedicating their life time after graduation to the profession of hospital pharmacy. Therefore, the second difficulty of the transforming of this profession is that we need a standard, to make sure that future clinical pharmacists are all highly trained and can provide high quality clinical services. For example, there is a pharmacy organization called NABP – National Association of Boards of Pharmacy. And before you become a licensed pharmacist, the candidate must pass the NAPLEX – North American Pharmacy License Exam.

The third question is how to teach these young students, with the intention to make them have the fundamental knowledge required to provide clinical pharmacy services. What services we can provide are dependent on what we have learnt from colleges. A pharmacist who lacks the knowledge of pharmacotherapy is not able to discuss the therapeutic regimen with his/her patients, nor his/her colleagues. Although we have strong background of pharmacology, but the background is limited to the pharmacologic action. Actually, the other two most important aspects of pharmacology are the physiologic effect and the clinical outcome. In my opinion, the curriculums of pharmacy colleges and schools need upgrading, to adapt the new role of pharmacists, to meet the necessaries required by our patients, our healthcare colleagues, and our society.

In addition to the basic knowledge, another question is how to train pharmacy students, in order to enable them the basic abilities and skills required by this profession. The key prerequisites to provide clinical pharmacy services is based on the clinical abilities and skills, or more precisely, the pharmacy practice experiences. Clinical pharmacy is not only a discipline of research or science, but also one involved with daily clinical practice.

The Management of Hyponatremia

October 26, 2014 Critical Care, Pharmacotherapy, Therapeutics No comments ,

The human body tightly regulates blood volume and plasma osmolality as both are essential for normal cellular function. Blood volume is important because it is a determinant of effective tissue perfusion which is required to deliver oxygen and nutrients to and remove metabolic waste products from tissues.

The homeostatic mechanisms for controlling blood volume are focused on controlling sodium balance.

Hyponatremia is defined as serum sodium less than 135 mEq/L. Hyponatremia is the most common electrolyte abnormality encountered in clinical practice.


The Genesis of Osmosis

When a substance is dissolved in water, the concentration of water molecules in the solution is less than that in pure water, because the addition of solute to water results in a solution that occupies a greater volume than dose the water alone. If the solution is placed on one side of a membrane that is permeable to water but not to the solute, and an equal volume of water is placed on the other, water molecules diffuse down their concentration (chemical) gradient into the solution. This process – the diffusion of solvent molecules into a region in which the membrane is impermeable – is called osmosis.

The tendency for movement of solvent molecules to a region of greater solute concentration can be prevented by applying pressure to the more concentrated solution. The pressure necessary to prevent solvent migration is the osmotic pressure of the solution. Just like shown in picture below.

Screen Shot 2014-10-26 at 3.00.36 PM


Sodium and Water Homeostasis

60% of total body water is located intracellularly, whereas 40% is contained in the extracellular space. Sodium and its accompanying anions, chloride and bicarbonate, comprise more than 90% of the total osmolality of the extracellular fluid (ECF), whereas intracellular osmolality is primarily dependent on the concentration of potassium and its accompanying anions (mostly organic and inorganic phosphates). Most cell membranes are freely permeable to water.

The process – the diffusion of solvent molecules into a region in which there is a higher concentration of a solute to which the membrane is impermeable – is called osmosis. The tendency for movement of solvent molecules to a region of greater solute concentration can be prevented by applying pressure to the more concentrated solution. The pressure nenessary to prevent solvent migration is the osmotic pressure of the solution.

However, the body fluids are not ideal solutions. Thus it is actually the effective concentration (activity) in the body fluids rather than the number of equivalents of an electrolyte in solution that determines its osmotic capacity. This is why, for example, 1 mmol of NaCl per liter in the body fluids contributes somewhat less than 2 mOsm of osmotically active particles per liter. The more concentrated the solution, the greater the deviation from an ideal solution.

Solutes that cannot freely cross cell membranes are referred to as effective osmoles. The concentration of effective osmoles in the ECF determines the tonicity of the ECF, which directly affects the distribution of water between the extra– and intracellular compartments. Addition of an isotonic solution to the ECF will result in no change in intracellular volume since there will be no change in the effective osmolality of the ECF. Addition of a hypertonic solution to the ECF, however, will result in a decrease in cell volume, whereas addition of a hypotonic solution to the ECF will result in an increase in cell volume. Generally, the plasma osmolality can be estimated as:

Sosm = (2 x SNa) + (Bglucose/18) + (BUN/2.8)

The volume of the ECF is determined primarily by the total amount of osmotically active solute in the ECF (sodium, chloride, and bicarbonate). Generally the amount of sodium in the ECF is the most important determinant of ECF volume.

The regular of extracellular fluids is based on vasopressin (ADH) and renin-angiotensin system. The detail regulation mechanisms of ADH and RAS can be found here (http://www.tomhsiung.com/wordpress/2014/03/the-regular-of-extracellular-fluids-adh-secretion-and-renin-angiotensin-system/).


Pathophysiology

Hyponatremia can be associated with normal, increased, or decreased plasma osmolality. Hyponatremia in patient with normal serum osmolality can be caused by hyperlipidemia or hyperproteinemia. Historically this form of hyponatremia is termed pseudohyponatremia since it cause is the method of serum sodium concentration measurement, which is a laboratory artifact and is uncommon today.

Hyponatremia associated with increased serum osmolality, termed hypertonic hyponatremia, suggests the presence of excess, nonsodium-effective osmoles in the ECF. This is most frequently encountered in patients with hyperglycemia. Elevated concentrations of glucose provide effective plasma osmoles, resulting in diffusion of water from the cells into the extracellular compartment thereby expanding the ECF, which results in decrease in the serum sodium concentraion. For every 100 mg/dL increase in the serum glucose concentration, the serum sodium level decreases by 1.7 mEq/L, and the serum osmolality increases by 2 mOsm/kg.

Hyponatremia associated with decreased plasma osmolality is the most common forum of hyponatremia. Hypotonic hyponatremia can be divided into three categories: hypotonic hyponatremia with, decreased, increased, or normal ECF volume.

Hypovolemic Hypotonic Hyponatremia

Most patients with ECF volume contraction lose fluids that are hypotonic relative to plasma and thus can be transiently hypernatremiac. This includes patients with fluid losses caused by diarrhea, excessive sweating, and diuretics. This transient hypernatremic hyperosmolality results in osmotic release of AVP and stimulation of thirst (also you can find detail information about regulation mechahnisms of ADH in the post I have mentioned above earlier). If sodium and water losses continue, more AVP is released as a result of hypovolemia. Patients who drink water or who are given hypotonic fluids intravenously retain water and develop hyponatremia. These patients typically have a urine osmolality greater than 450 mOsm/kg, reflecting the presence of AVP and formation of a concentrated urine. The urine sodium concentration is <20 mEq/L when sodium losses are extrarenal (the decreased effective circulatory volume enhances the reabsorption of sodium in kidneys), as in patients with diarrhea, and >20 mEq/L in patients with renal sodium losses, as occurs in the setting of diuretic use or adrenal insufficiency.

Second, the decreased effective circulating volume due to lose of ECF fluids stimulates the release of AVP.

Hypotonic hyponatremia is relatively common in patients taking thiazide diuretics (but infrequently with loop diuretics since less AVP-induced water reabsorption by disturbing countercurrent mechanism). Thiazide-induced hyponatremia is usually mild, but can occasionally be severe and symptomatic. The pathophysiology is as the same as I have described above (decrease effective circulating volume). It typically develops within 2 weeks of the initiation of therapy, but can occur late in therapy, particularly if there has been a recent increase in the diuretic dose or other causes of hyponatremia develop.

Euvolemic Hypotonic Hyponatremia

Euvolemic hypotonic hyponatremia is associated with a normal or slightly decreased ECF sodium content and increased total body water and ECF volume. The increase in ECF volume is usually not sufficient to cause peripheral or pulmonary edema, and thus patients appear clinically euvolemic.

Euvolemic hyponatremia is most commonly the result of SIADH release (syndrome of inappropriate antidiuretic hormone secretion), which abnormal increased release of AVP causes excessive water reabsorption in kidneys. Urine is concentrated with urin sodium usually greater than 20 mEq/L.

Hypervolemic Hypotonic Hyponatremia

Hyponatremia associated with an increase in ECF (different with euvolemic hypotonic hyponatremia which is associated with increased total body water and ECF volume but not sufficient to cause peripheral or pulmonary edema) occurs in conditions in which renal sodium and water excretion are impaired. Hypervolemic status is caused by cirrhosis, congestive heart failure, or nephrotic syndrome. But these disease status also cause decreased effective circulating volume (low perphieral perfusion), which stimulates the release of AVP.


The Management of Hypotonic Hyponatremia

Before make correction of hypotonic hyponatremia one should balancing the risks of the hyponatremia versus the risk of osmotic demyelination syndrome. In general, patients who acutely developed moderate to severe hyponatremia and/or patients who have severe symptoms are at greatest risk and potentially benefit most from more rapid correction of their hyponatremia.

The management of hypotonic hyponatremia consists of acute or severe symptomatic hypotonic hyponatremia, and nonemergent hypotonic hyponatremia. Here we just discuss acute or severe symptomatic hypotonic hyponatremia.

First it is important to treat the underlying cause of hyponatremia.

For all hypovolemic hypotonic hyponatremia, the goal of treating patients is to resolve the underlying cause of the sodium and ECF deficits, and safely correct the hyponatremia.

For all hypervolemic and euvolemic hypotonic patients the goal of treatment depends on the underlying cause of the hyponatremia and the severity of the patient’s symptoms.

For acute or severe symptomatic hypotonic hyponatremia the goal is to correct the hypotonicity with aggressive therapy enough to control the symptoms.

Here we discuss a little about the brain’s compensation to hypotonic hyponatremia. The presence of the neurologic symptoms and their severity depend on both the magnitude of the hyponatremia and the rate at which the hyponatremia developed. The magnitude of hyponatremia is directly associated with the water movement into brian cells increasing as serum osmolality decreases. The rate of osmolality change is also important because brain cells are able to adjust their intracellular osmolality to minimize cellular volume changes in response to volume changes, but time is required for this adaptation to occur.

When a decline in plasma osmolality causes movement of water into brain cells, sodium, potassium, and organic osmolytes move out of the cells to decrease intracellular osmolality and minimize intracellular water movement. But this compensatory mechanism takes time and maximal compensation for a decrease in plasma osmolality typically requires up to 48 hours. Thus acute changes in plasma osmolality are not compensated for instantaneously and are more likely to be associated with symptoms.

Attention must be paid to that in all cases one should avoid an increase in the serum sodiuim concentration of more than 12 mEq/L in 24 hours.

If the serum sodium is observed to be increasing at a rate greater than 12 mEq/L per day, the infusate should be changed to 0.45% sodium chloride, and the infusion rate set to one that approximates urine output to slow the rate of increase in the serum sodium concentration.

A patient who has or is at high risk of experiencing severe symptoms caused by hypotonic hyponatremia should receive either 3% (513 mEq/L of sodium) or 0.9% (154 mEq/L of sodium) sodium chloride solution until severe symptoms resolve. Resolution of severe symptoms frequently requires only a small, 5% increase in serum sodium, although some suggest that the initial target should be to increase serum sodium to approximately 120 mEq/L.

To ensure the net effect of solute-free water excretion (ensure net increase in total effective osmoles) after the infusate the concentration of sodium in the infusate must exceed the sum of the sodium and potassium concentration in the urine.

For instance, patients with SIADH often have urinary concentrations of osmotically effective urine cations that exceed the sodium concentration of 0.9% sodium thus in this case we should give these patients 3% sodium chloride. However, when the urine osmolality exceeds 300 mOsm/kg, it is generally advisable to add an intravenous loop diuretic, not only to increase the excretion of solute-free water (since we use 3% NaCl the sodium concentration in the infusate is much higher than it would be expected in the urine after addition of loop diuretics), but also to prevent volume overload possibly resulting from infusion of hypertonic sodium chloride.

Patients with hypovolemic hypotonic hyponic hyponatremia can be treated with 0.9% sodium chloride. In contrast to patients with SIADH, patients with this condition avidly reabsorb sodium throughout the nephron when the effective circulating blood volume is decreased. Thus the urine osmolality is primarily comprised of urea, and the concentration of urine sodium is often less than 20 mEq/L, which is substantially less than the sodium concentration in 0.9% sodium chloride solution. Use of 3% sodium chloride solution will also effectively correct hyponatremia but its use should be reserved for situations requiring very rapid correction.

Once we decide to give infusate of 3% or 0.9% sodium chloride solution we should certain the right infusion regimen. There is a formula to estimate the change in SNa with 1 L of infusate.

Change in SNaith 1 L of infustate = [IVNa-S1Na] ÷ (BW + IVvol)

where S1Na = initial patient serum sodium concentration; IVNa = sodium concentration of infusate (154 mEq/L for 0.9% sodium chloride and 513 mEq/L for 3% sodium chloride); IVvol = 1 L of infusate; and BW= total body water.

Total boday water can be estimated as follows:

0.6 × body weight for children and men <70 years of age; 0.5 × body weight for men ≥70 years of age and females <70 years of age; and 0.45 body weight for women ≥70 years of age.

In the presence of symptoms, the serum sodium should be increased by approximately 1.5 mEq/L per hour over the first 2 to 4 hours or until symptoms have resolved. Thus for the first 2 to 4 hours the rate of infusion should be 114 ml per hour of 3% sodium chloride and then 23 to 31 ml per hour for the next 20 to 22 hours respectively.


Evaluation of Therapeutic Outcome

Patients with severely symptomatic hypotonic hyponatremia should be admitted to the intensive care unit or to a highly monitored setting for close monitoring of neurologic and volume status. Serial physical examinations of the heart, lungs, and neurologic status should be performed several times over the initial 12 hours of hospitalization. The serum sodium concentration should be measured every 2 to 4 hours, and the urine osmolality, sodium, and potassium should be measured every 4 to 6 hours over the first day of therapy. The rate of administration of the infusate should then be adjust to avoid exceeding a rise in the serum sodium greater than 12 mEq/L per 24 hours.

The Management of Nonemergent Hypotonic Hyponatremia

October 26, 2014 Pharmacotherapy, Therapeutics No comments

The desired outcome of nonemergent hypotonic hyponatremia is the same as described in the former post. For all hypovolemic hypotonic hyponatremia, the goal of treating patients is to resolve the underlying cause of the sodium and ECF deficits, and safely correct the hyponatremia. For all hypervolemic and euvolemic hypotonic patients the goal of treatment depends on the underlying cause of the hyponatremia and the severity of the patient’s symptoms.


Nonemergent Hypovolemic Hypotonic Hyponatremia

Most patients with hypovolemic hypotonic hyponatremia do not require rapid correction of their hyponatremia since they are either asymptomatic or have only mild-to-moderate symptoms. Many of these patients are at higher risk of developing osmotic demyelination syndrome if serum sodium correction occurs too rapidly because they have chronic hyponatremia that has been maximally compensated for by the brain’s osmotic adaptation.

Here we discuss a little about the brain’s compensation to hypotonic hyponatremia. The presence of the neurologic symptoms and their severity depend on both the magnitude of the hyponatremia and the rate at which the hyponatremia developed. The magnitude of hyponatremia is directly associated with the water movement into brian cells increasing as serum osmolality decreases. The rate of osmolality change is also important because brain cells are able to adjust their intracellular osmolality to minimize cellular volume changes in response to volume changes, but time is required for this adaptation to occur.

When a decline in plasma osmolality causes movement of water into brain cells, sodium, potassium, and organic osmolytes move out of the cells to decrease intracellular osmolality and minimize intracellular water movement. But this compensatory mechanism takes time and maximal compensation for a decrease in plasma osmolality typically requires up to 48 hours. Thus acute changes in plasma osmolality are not compensated for instantaneously and are more likely to be associated with symptoms.

When direct treatment of the hyponatremia is justified, a 0.9% solution of sodium chloride should be used since this solution effectively replaces both the sodium and water deficits that characterize these patients and presents a lower risk of an excessive rate of correction than 3% sodium chloride solution.

Treatment Strategy

The therapeutic approach for nonemergent hypovolemic hypotonic hyponatremia is to correct the patient’s ECF volume deficit and to restore effective circulatory volume. If possible, underlying condition should be corrected too. So first step is to estimate the patient’s ECF voume deficit. Generally the ECFVd can be estimated based on the patient’s sex, change in body weight, and age. Active correction of hypovolemic hypotonic hyponatremia is usually best accomplished with 0.9% sodium chloride solution as these patients have both sodium and water deficits.

The total body water can be estimated as: 0.6 × body weight for children and men <70 year old; 0.5 × body weight for men >70 years of age and femals <70 years of age; and 0.45 × body weight for women ≥70 years of age. And due to the fact that one third of totoal body water is in extracellular space so the ECF volume can be estimated via multiplying total body water volume by 0.33 (33%).

Since the initial goal is to restore effective circulating volume, it might be necessary to infuse 0.9% sodium chloride at 200 to 400 ml per hour until symptoms of hypovolemia moderate. Then the infusion rate can be decreased to 100 to 150 ml per hour so that the serum sodium level increases by no more than 12 mEq/L over the initial 24 hours. Infusion of 0.9% sodium chloride at rates greater than 250 ml/h should be used cautiously in patients with history of left ventricular dysfunction or renal insufficiency. And it is important to recognize that the rate of increase in the serum sodium concentration can substantially increase once hypovolemia has been corrected if infusion rates are not decreased (Once the ECF volume (more accurately, the effective circulatory volume) is restored, AVP secretion will cease, and a rapid water diuresis can ensue, which can potentially result in an increase in the serum sodium at a rate greater than 12 mEq/L per 24 hours).

If the serum sodium is observed to be increasing at a rate greater than 12 mEq/L per day, the infusate should be changed to 0.45% sodium chloride, and the infusion rate set to one that approximates urine output to slow the rate of increase in the serum sodium concentration.

Evaluation

Patients presenting with evidence of volume depletion should be reexamined frequently during the initial few hours of therapy. The serum sodium concentration should be measured every 2 to 4 hours to allow timely adjustment of the rate and composition of intravenous fluids to avoid an increase in the serum sodium greater than 12 mEq/L per 24 hours. Intravenous 0.9% sodium chloride should be administered judiciously in patients with a history of congestive heart failure or renal insufficiency, with frequent assessments of the cardiopulmonary examination so the infusion rate can be appropriately decreased at the earliest sign of pulmonary congestion.

Example

Let’s see an example. A 56-year-old woman who was started on hydrochlorothiazide 10 days ago for the treatment of hypertension. Today she presents with complaints of mild nausea and “feeling dizzy” when she stands up. She is 173 cm tall and weighed 62 kg at 10 days ago and 55.5 kg at now and the serum sodium concentration at present is 125 mEq/L. What should we do to treat this patient. Obviously, this patient loses her ECF volume due to hydrochlorothiazide because her weight changed from 62 to 55.5 kg in 10 days. The loss of ECF volume causes orthostatic hypotension and decreased effective circulatory volume, which stimulates the release of AVP. Here I think it is better to get her urine dialysis to check if the urine were concentrated, which could confirm the increased secretion of AVP.

First is to estimate her ECF volume deficit. The ECF volume deficit equals the ECF volume 10 days ago minus the ECF volume at present. Which equals, 62 × 0.5 L/kg × 0.33 – 55.5 × 0.5 L/kg × 0.33, 1 L. Then we use 0.9% sodium chloride solution to restore the ECF volume and the estimated increase in serum sodium of 1 L of 0.9% sodium chloride of this patient equals, (154 mEq/L – 125 mEq/L) ÷ (0.5 L/kg × 55.5 +1 L), 1 mEq/L. That is if we give her 1L of 0.9% sodium chloride her serum sodium concentration would increase by 1 mEq/L. And we should give her 10 L of 0.9% sodium chloride solution to restore the serum concentration of sodium to 135 mEq/L.

However, after we give her 1 L of 0.9% sodium chloride, her ECF volume and the effective circulatory volume would restore to normal and as a result the release of AVP would cease, which would cause abundant free water loss or rapid water diuresis and a substantially increase in rate of the correction of serum sodium concentration. So the patient’s serum sodium concentration would increase rapid and we must slow down the drip rate of 0.9% sodium chloride infusate. If we observe that her serum concentration of sodium increases at a rate greater than 12 mEq/L per 24 hours we should stop 0.9% sodium chloride and instead use 0.45% sodium chloride at a rate equaling to urine output (In assumption, after giving her 1 L of 0.9% NaCl we continue to give her the remaining 9 L of 0.9% NaCl. However, we find that her serum sodium concentration increasing at rate of 0.6 mEq/L per hour [14.4 mEq/L per 24 hours] we should change the 0.9% NaCl to 0.45% NaCl at a rate of approximate the urine output).


Nonemergent Euvolemic Hypotonic Hyponatremia

Again firstly, it is important for both the short- and long-term management of the patient to treat the underlying cause of hyponatremia. The benefit of rapid correcting acute developed moderate to severe hyponatremia and risk of osmotic demyelination syndrome should be balanced. Active correction of euvolemic hypotonic hyponatremia in patients who do not require rapid correction is usually best accomplished by water restriction.

Active correction of euvolemic hypotonic hyponatremia in patients who do not require rapid correction is usually best accomplished by water restriction. Under the condition of chronic hyponatremia, the combination of adaptive decrease in intracellular osmolality and rapid increase in serum osmolality results in excessive movement of water out of the brain cells, intracellular volume depletion, and thereby an increased risk of osmotic demyelination syndrome.

The therapeutic goal of euvolemic hypotonic hyponatremia is to induce negative water balance by restricting water intake to less than 1,000 to 1,200 ml/day, such that water loss from insensible source and from obligate urine and fecal losses exceed intake. In general, the daily water in consists of 850 ml from foods and 350 ml from oxidative reactions. The daily water out consists of 900 ml in skin and lung losses, 200 ml in stool, and 500 ml in urine.

Patients who are unable to restrict water sufficiently to maintain the serum sodium greater than 120 to 125 mEq/L can be treated by increasing solute intake with sodium chloride and/or loop diuretics. The goal is to increase the daily solute intake and excretion to approximately 900 mOsm per day (for the kidneys to eliminate an “X” amount of solutes, a certain volume of water must be excreted. And sodium chloride or urea tablets increase the obligatory daily solute excretion, which augments the capacity for renal water excretion). To excrete more net water (by limiting the formation of the medullary concentration gradient, or “ countercurrent mechanism“) and to prevent extracellular volume expansion and volume overload (due to enhanced active solute intake), a loop diuretic should be administered concurrently.

Demeclocycline and ADH receptor antagonists such as vaptans could be used too in the setting of euvolemic hypotonic hyponatremia but before administering these drugs, cautions should be taken to understand the risk and toxicity of these drugs, which can be found in Drug Information Center at mediawiki.tomhsiung.com.

Monitor

The serum sodium level should be measured every 24 to 48 hours after the water restriction is initiated until it stablizes at a concentration of greater than 125 mEq/L. A continued decline in the serum sodium level would indicate either nonadherence to the prescribed restriction or the need for a more stringent restriction.

Once the serum sodium has stablilized above 125 mEq/L, patients should then be seen every 2 to 4 weeks to assess neurologic status and to obtain serum and urine for sodium, potassium, and osmolality. Again, attention should be given to volume status.


Nonemergent Hypervolemic Hypotonic Hyponatremia

it is important for both the short- and long-term management of the patient to treat the underlying cause of hyponatremia. The benefit of rapid correcting acute developed moderate to severe hyponatremia and risk of osmotic demyelination syndrome should be balanced. Active correction of hypervolemic hypotonic hyponatremia in patients who do not require rapid correction is usually best accomplished by water restriction.

The initial treatment goals for patients with asymptomatic or minimally symptomatic hypotonic hyponatremia and and expanded ECF volume include achieving a negative water balance while minimizing rapid changes in cell volume until the serum sodium is greater than 125 mEq/L. This entails correction of the underlying cause when possible, as well as restriction of water intake to a volume less than 1,000 to 1,200 ml per day. The underlying causes please check pathophysiology of hypotonic hyponatremia at http://www.tomhsiung.com/wordpress/2014/04/the-management-of-hyponatremia/.

Other strategies including vasopresssin receptor antagonists as same as euvolemic hypotonic hyponatremia. But demeclocycline should be avoid since these underling causes of hypervolemic hypotonic hyponatremia are related to renal sodium and water excretion impairment.

Monitor

Patients should initially be evaluated on a daily basis for volume expanding effects such as lung congestion, ascites, peripheral edema etc, and signs or symptoms of hyponatremia. The serum sodium concentration should be measured every 24 hours until it stabilized above 125 mEq/L following initiation of water restriction.

Patients should then be assessed 1 week following discharge, and then every 2 to 4 weeks to assess compliance with the water restriction and other treatment measures, volume status, and hyponatremia-related symptoms.

How to install Mavericks 10.9.1 on PC

October 24, 2014 Hackintosh No comments , , ,

Well, I am a lucky guy today. I successfully installed Mavericks 10.9.1 on my PC. The brief device list of my PC is below.

CPU: AMD FX6300

Mother Board: Asus M5A97 R2.0

Graphic Card: Sapphire HD7870 2GB

Wireless Card: TP-link TL-WN851N

Hard Disk: Seagate 80 GB

OK. Let’s begin. First, the install process is based on the guide from TonyMacX86 (http://www.tonymacx86.com/374-unibeast-install-os-x-mavericks-any-supported-intel-based-pc.html). Notice that the methods of guides from TonyMacX86 are all designed for PCs with Intel-based CPUs. So how did I make it? I am with a cpu of AMD FX6300.

So this is what I have found via searching the Internet with key words of “FX6300” and “Hackintosh”. The original site is from Reddit (http://www.reddit.com/r/hackintosh/comments/1yhx4p/amd_fx6300_osx_mavericks_1091_hackintosh/). Now I quote the post without any modification below.

[AMD FX-6300] OSX Mavericks 10.9.1 Hackintosh Installation Successful! Fully operational! [Audio, Internet, GPU, iCloud, iMessage] (self.hackintosh)

submitted   by 38darkness42

Alright guys so I browse these forums every so often because I love Hackintoshing and I do it on YouTube alot as well. I recently upgraded my PC and after two days of tinkering with my system I was able to get a fully working Hackintosh! Heres my specs:

Processor: AMD FX-6300

Motherboard: Gigabyte 990-FXA-UD3

GPU: GeForce GTX 760 (Worked out of the box, no additional kexts!)

PSU: Thermaltake TR2-700 700W PSU

RAM: 4GB Memory

Storage: 60GB SSD (used as Windows boot drive) 500GB Hard Drive (Used for additional files, completely wiped for mac)

It was a tedious process however with some help of a friend I was able to get it running pretty smoothly. Here’s my process:

1) I initially was going to use Niresh’s 10.9 distro, however I decided since I have a MacBook I could install Tonymacx86’s Unibeast and then replace the Mach_kernel with a modified AMD Mach_Kernel

2) Then, I booted into my USB drive and used the boot flags “GraphicsEnabler=No npci=0x3000 -v” Booted into installation flawlessly. Thanks to the modified AMD kernel I was able to avoid getting a kernel panic here.

3) Partitioned/installed on my 500GB Hard Drive. Nothing to say here really, just format as Mac OS X Extended (Journaled) and I was good to go.

(keep in mind that no kexts and a bootloader is not on the partition yet, I will have to do that post-installation)

4) Install went smooth as expected, but when I tried to boot into my Mac I realized that every time (I tried about three times) It would just reboot and start over again.

5) I make tutorials on YouTube. And I remember that in my Mountain Lion tutorial I actually had to copy and paste the kernel that I used in the installation to my partition to boot. So I thought it was worth a shot. I went into terminal, typed “cp /mach_kernel /Volumes/Macintosh” (Macintosh being my partition name)

6) Restarted the boot and it booted flawlessly. Once again using the flags “GraphicsEnabler=No npci=0x3000 -v”

7) Post installation I was able to install my ethernet and tried to install my alc audio kext, but it didn’t work. That wasn’t top of my priorities then, I needed a bootloader. Using the DSDT-Free setup Unibeast offered, I always kept getting a kernel panic every time I booted. Then I tried to boot with “-x” for a safe boot and it was able to get past the conflicting kexts. I deleted my AppleIntelCPUPowerManagement.kext and AppleIntelCPUPowerManagementClient.kext and it booted up no problem once again.

8) After booting and everything almost done, I downloaded the newest Chameleon bootloader and rebooted. Once again, worked flawlessly.

9) Finally, I installed VoodooHDA for my audio. It worked, however the volume was really quiet. I had to edit a .plist string to fix it. My microphone malfunctions alot, and to my friends who I talk to on Skype say I sound like a robot. Hopefully I can fix this in the near future.

Overall I’m pretty proud of the outcome and hopefully I’ll make a tutorial on how to install 10.9 for AMD processors sometime soon.

Here’s a screenshot of some of the system info:

http://imgur.com/O7yryc9

If anyone has any tips/tricks/questions please feel free to leave a comment! Thanks for reading.

Here’s a list of kexts I used:

AMD Kernel: http://www.osx86.net/files/file/3657-amd-fx-109-mavericks-kernel-nvidia-work/

Audio Kext: http://www.osx86.net/files/file/1194-voodoohda-2-8-4-pkg-installer/ (NOTE: Keep in mind if you use this kext you must delete/disable the AppleHDA Audio kext to prevent a kernel panic. However, when I installed the Package it also installed the AppleHDA disabler kext. So I didn’t have to worry about that.)

Bootloader: http://www.osx86.net/files/file/3818-chameleon-22svn/

Once again, video worked out of the box, GPU Acceleration/etc is great, I can play League of Legends on a solid 40FPS with everything on Ultra High however in Windows I usually hit 130-200 FPS. It’s not that much of a resource-demanding game and I’m not sure why my Hackintosh is getting such low results, I’m going to look into it.

I want to emphasize that (1). make sure there is only one USB device inserting on the mother board, or you might fail to boot in with the USB disk. (2) make sure that the USB disk is inserted on the USB2.0 port, otherwise you might be fail to boot in with the USB disk too. (3) You have to get the root user privilege to replace the Mach_kernel file located in the root directory of the USB disk (only the root user have the write and read privileges). And finally, the most important is the modified AMD Mach_kernel. It’s here (http://bbs.pcbeta.com/viewthread-1458974-1-1.html).

OK, I wish you guys succeeding.

Fundamentals of Lung Auscultation

October 11, 2014 Clinical Skills, Critical Care No comments ,

Generally, respiratory can be divided into two process: inspiration and expiration. As a result the sounds generated by breath can be along with the inspiration or expiration process. Below we first talk about the normal respiratory sounds, thereafter we focus on abnormal respiratory sounds.

Normal respiratory sounds include tracheal sound, “vesicular” sounds. Abnormal respiratory sounds include musical sound (stridor, wheeze) and nonmusical sounds (crackles, pleural friction rub, and squawk). To make the auscultation of lung sounds useful, clinicians should not only identify the characteristics of them, but also the intensity. I summarize that clinical should identify and record these parameters of the lung sounds including: [1].characteristcs, [2].intensity, [3].the time of occurring during the respiratory process (inspirati  on, expiration; early, mid, or late phase), [4].persisting time, [5].whether the sounds changing along with the patient’s body position, [6].whether the sounds changing after coughing, and [7].the location (all over the chest, localized sounds, etc).

Normal Respiratory Sounds

The traditional nomenclature for lung sounds suffers from imprecision. Therefore, we have adopted the terminology proposed by the ad hoc comittee of the international Lung Sounds Association. In this classification of lung sounds, the term “rale” is replaced by “crackle”, since the adjectives often used to qualify rales can be misleading with regard to the means by which rales are produced. “Crackle” can be defined acoustically and does not suggest any means or site of generation.

Tracheal Sounds

Normal tracheal sounds characteristically contain a large amount of sound energy and are easily heard during the two phases of the respiratory cycle. Tracheal sounds are produced by turbulent airflow in the pharynx, glottis, and subglottic region. Listening to tracheal sounds can be useful in a variety of circumstances. First, the trachea carries sound from within the lungs, allowing auscultation of other sounds without filtering from the chest cage. Second, the characteristics of tracheal sounds are similar in quality to the abnormal bronchial breathing heard in patients with lung consolidation. Third, in patients with upper-airway obstruction, tracheal sounds can become frankly musical, characterized as either a typical stridor or localized, in tense wheeze. Finally, monitoring tracheal sounds is a noninvasive means of monitoring patients for the sleep apnea syndrome, although for practical reasons such monitoring cannot be performed by means of auscultation with a stethoscope.

Lung, or “Vesicular,” Sounds

The sound of normal breathing heard over the surface of the chest is markedly influenced by the anatomical structures between the site of sound generation and the site of auscultation. The idea that “vesicular” sound is produced by air entering the alveoli (“vesicles”) is incorrect. Indeed, modern concepts of physiology indicate that in the lung periphery gas molecules migrate by means of diffusion from parts of the lung reached through bulk flow, a silent process. Most important, studies support the idea of a double origin, with the inspiratory component generated within the lobar and segmental airways and the expiratory component coming from more central sources. However, normal lung sounds are heard clearly during inspiration but only in the early phase of expiration.

As we mentioned previously, not only the characteristics of sounds but also the intensity of them are critical and clinically, a decrease in sound intensity is the most common abnormality. Mechanistically, this loss of intensity can be due to a decrease in the amount of sound energy at the site of generation, impaired transmission, or both. Sound generation can be decreased when there is a drop in inspiratory air flow. The decrease in the intensity of breath sounds may be permanent, or reversible. Transmission can be impaired by intrapulmonary or extrapulmonary factors. Intrapulmonary factors include disruption of the mechanical properties of the lung parenchyma, or the interposition of a medium between the source of sound generation and the stethoscope that has a different acoustic impedance from that of the normal parenchyma.

Incidentally, the development of lung consolidation, which occurs in pneumonia, results in decreased breath sounds only if the embedded airways are blocked by inflammation or viscous secretions. If instead the airways are patent, sound transmission is actually improved, increasing the expiratory component. This effect is characterized as “bronchial breathing”, which corresponds to the air bronchogram on chest radiographs.

Abnormal Respiratory Sounds

Abnormal respiratory sounds can be divided into two categories including musical sounds, and nonmusical sounds, where musical sounds consist of stridor and wheeze, while nonmuscial sounds contain crackles, pleural friction rub, and the squawk.Sound Analysis in Lung Auscultation

Stridor

Stridor is a high-pitched, musical sound produced as turbulent flow passes through a narrowed segment of the upper respiratory tract. It is often intense, being clearly heard without the aid of a stethoscope. Usually stridor is inspiratory, but it can also be expiratory or biphasic.

Wheeze

Wheeze usually persists for more than 100 msec, allows its musical quality to be discerned by the human ear. It is probably incorrect to credit high-pitched wheezes to the narrowing of peripheral airways and low-pitched wheezes to the narrowing of central airways. Purportedly, wheezes are formed in the branches between the second and seventh generation of the airway tree by the coupled oscillation of gas and airway walls that have been narrowed to the point of apposition by a variety of mechanical forces. In addition, the model incorporates two principles: first, that although wheezes are always associated with airflow limitation, airflow can be limited in the absence of wheezes, and second, that the pitch of an individual wheeze is determined not by the diameter of the airway but by the thickness of the airway wall, bending stiffness, and longitudinal tension.

Wheezes can be inspiratory, expiratory, or biphasic. Wheezes are not pathognomonic of any particular disease. It can be heard all over the chest, or only locally. Wheezes may be absent in patients with severe airway obstruction (intensity) since more severe the obstruction the lower the likelihood of wheeze. Finally, a sound – the rhonchus, is considered to be a variant of the wheeze, which is responsible for its resemblance to the sound of snoring on auscultation. However, unlike the wheeze, the rhonchus may disappear after coughing, which suggests that secretions play a role.

Crackles

Crackles are short, explosive, nonmusical sounds heard on inspiration and sometimes during expiration. Two categories of crackles have been described: fine crackles and coarse crackles. On auscultation, fine crackles are usually heard during mid-to-late inspiration, are well perceived in dependent lung regions, and are not transmitted to the mouth. Uninfluenced by cough, fine crackles are altered by gravity, changing or disappearing with changes in body position.

The most likely mechanism for the generation of fine crackles is the sudden inspiratory opening of small airways held closed by surface forces during the previous expiration.

Coarse crackles tend to appear early during inspiration and throughout expiration and have a “popping” quality. They may be heard over any lung region, are usually transmitted to the mouth, can change or disappear with coughing, and are not influenced by changes in body position. Coarse crackles are probably produced by boluses of gas passing through airways as they open and close intermittently.

The significance of crackling sounds is probably not due to secretions, except of the crackling sounds heard in moribund patients, or in patients with abundant secretions.

Pleural Friction Rub

In healthy persons, the parietal and visceral pleura slide over each other silently. In persons with various lung diseases, the visceral pleura can become rough enough that its passage over the parietal pleura produces crackling sounds heard as a friction rub. In our experience, this sound is more prominent on auscultation of the basal and axillary regions than on auscultation of the upper regiions. One explanation for this difference is the fact that the basal regions lie on the steep portion of the static pressure-volume curve, whereas the upper regions lie on the flat portion of the curve. Thus, for a given change in transpulmonary pressure, the basal regions undergo greater expansion.

Typically, the pleural friction rub is biphasic, with the expiratory sequence of sounds mirroring the inspiratory sequence. The reason for the genesis of pleural friction rub is that the sudden release of trangential energy from a lung surface that is temporarily prevented from sliding because of a frictional force between the two pleural layers. Generally, pleural friction rubs are heard in inflammatory diseases or maliganant pleural diseases.

Mixed Sound – The Squawk

Also called “short wheeze” or “squeak,” the squawk is a mixed sound, containing musical and non-musical components. Squawks are typically heard from the middle to the end of inspiration in patients with interstitial diseases, especially hypersensitivity pneumonitis. However, they are not pathognomonic of this condition, having also been documented in other situations. The mechanism underlying the production of squawks is not entirely known, but according to one theory, they are produced by the oscillation of peripheral airways (in deflated lung zones) whose walls remain in apposition long enough to oscillate under the action of the inspiratory airflow.