Aneuploidy Screening in the News

Yesterday, I heard on NPR that the New England Journal of Medicine published an article about a new prenatal aneuploidy screening test, maternal cell-free plasma DNA (cfDNA), that may replace the standard screening test in place. Lucky for me, I have access to journal articles at the hospital and I wanted to summarize what I read.

DNA Sequencing versus Standard Prenatal Aneuploidy Screening

The use of cfDNA as a screening test for aneuploidy started back in 2011 after clinical validation studies all showed high sensitivity, specificity and negative predictive value for detection of the most common aneuploidies (trisomy 21 and 18). The studies had taken plasma samples retrospectively from patients with known karyotypes or prospectively from high risk patients. The results of the studies allowed the test be integrated into the clinical practice and used specifically for high-risk women. The question still remained, though, of how effective the screening test was in low-risk patients. A few studies had been conducted and showed promising results, however, they were conducted outside of the US and did not represent the approaches used in the US. The article published by the NEJM describes the results of the Comparison of Aneuploidy Risk Evaluation (CARE) which was a prospective, blinded study that compared the results of the cfDNA for aneuploidy with the current standard screening for trisomy 21 and 18 in the general population. The primary objective of the study was the comparison of false positive rates in each screening method.

Methods

Patients and Data Collection - The women enrolled for the study came from 21 different medical centers in 14 different states. To be eligible for the study, pregnant women needed to be at least 18 years old, carrying a fetus at least 8 weeks gestational age and had planned to undergo a standard prenatal serum screening test.

Clinical Outcomes - Patients were followed and categorized as having a live birth or a nonlive birth. For the live births, a pediatrician would examine the baby and document the baby as affected or not affected for trisomy 21 or 18. For nonlive births, cytogenetic testing or physical exam was performed.

Sample Collection, Sequencing and Aneuploidy Classification - At enrollment, a peripheral venous blood sample was obtained from all the participants. The sample was eligible for analysis if it was no more than 5 days old and contained at least 7 ml of blood. All the personnel were unaware of the clinical data and outcomes. For autosomal aneuploidy of chromosome 21, 18 and 13, samples with a normalized chromosome value of 4.0 or more were classified as affected and values of 3.0 or less classified as unaffected.

Aneuploidy Classification on Standard Screening - First trimester markers (pregnancy-associated plasma protein (PAPP-A), free beta subunit, human chorionic gonadotropin (hCG)) were combined with sonographic measurement of fetal nuchal translucency to formulate a risk score. Second-trimester serum values (maternal serum alpha-fetoprotein (MSAFP), hCG, unconjugated estriol and inhibin A) could be evaluated alone, in combination with first-trimester screening. Certified genetic counselors, who were unaware of the results of cfDNA and clinical outcomes, reviewed all the laboratory reports and trisomy 21 and 18 were classified as positive or negative for individual risk scores.

Results - Both methods (cfDNA and standard) detected all cases of aneuploidy but cfDNA had significantly lower false positive rates and higher positive predictive values for trisomy 21 and 18 than the standard screening test.

Discussion - This study set out to determine if this test would be valid in the general population rather than in high-risk women only and in the clinical setting in the US. The study was representative of the general population of women seen in clinical practice and showed that the performance of the cfDNA was better than the standard screening. The major advantage of using the cfDNA was the reduction of false positives! Although it is uncertain how cost-effective this test would be compared to the standard testing, the findings in the study merit further investigation as this may be overall, a superior test for fetal aneuploidy screening.

Intraoperative Neuromonitoring

Today on Anesthesiology, I was lucky to intubate a patient undergoing a laminectomy and lumbar spinal fusion. It was my first time participating in a neurosurgical case and I came across wealth of new information from my attending and resident! What I want to focus on is the topic of neuromonitoring during surgery.

First of all, why is neuromonitoring so important?

Patients undergoing neurologic procedures may be at increased risk from hypoxia and ischemia to vital neurologic structures. Since the patient is under anesthesia and is paralyzed for the procedure, one cannot simply check reflexes and ask a patient if they can feel this or that, move their toes and fingers etc. Intraoperative neuromonitoring is an excellent way to monitor the function of the central nervous and peripheral nervous system and may allow the early detection of ischemia and hypoxia before irreversible damage to the nervous system occurs. If a patient's action potential has diminished in amplitude or prolonged in duration, it is time to look at all of the factors that could be contributing. A good anesthesiologist will check all of the vitals (BP, HR, O2 saturation), the amount of volatile anesthestic the patient is receiving and if all of the monitors are in place. If everything looks good from the Anesthesiology side, the problem may be with the procedure itself (blood loss, swelling and compression of the spinal cord or peripheral nerves). 

What are the types of neuromonitoring used?

This can be divided into essentially the three "realms" that need to be monitored: motor, somatosensory and the overall brain function. 

Motor Evoked Potentials (MEP)

Through direct stimulation, motor pathways are assessed directly and measure the integrity of the motor neuron output by way of the action potential amplitude and duration. A nerve is stimulated and an outcome is measured from a muscle or a group of muscles. This is actually not monitored by the anesthesiologist but rather, a surgical tech who dedicates their entire time sitting by a machine and monitoring the evoked potentials (at least that's what was going on in our room). There are multiple different sites on the body where one could evoke action potentials such as...

• spinal cord stimulation - rarely used anymore
• transcranial motor evoked potentials - the cortex is stimulated through the scalp. This is what we used today. The pt had electrodes over his scalp (specifically over the appropriate area) and had evoked action potentials for the upper and lower extremities
• Cortical motor evoked potentials - the cortex is stimulated directly

Sensory Evoked Potentials (SEP) - Can be divided into somatosensory, visual and auditory

Somatosensory Evoked Potential (SSEP) is a very common form of neuromonitoring. Similar to MEP, it is measured action potential in response to stimulation of a cranial or peripheral sensory nerve (only in MEP it is motor and not sensory nerve stimulation). Common nerves stimulated are median, ulnar and posterior tibial nerves (our patient had ulnar stimulation).  SSEP  will help monitor the integrity of the sensory pathway (dorsal and spinothalamic tracts). 

Visual Evoked Potential (VEP) measures the action potential in response to stimulation of the optic nerve. A light is flashed into the patient’s eyes, and recordings are taken off the occipital area (need an EEG to record). An interesting point...our patient needed to be in the prone position for the procedure and his head was resting in a soft foam block with a hole in the middle for his face and eyes. My attending pointed out that we need to frequently check the patient's face to make sure that his eyes were not being compressed. The patient cannot move so if their eyes become compressed, they could swell and cause damage to the optic nerve or artery! It obviously wouldn't be a good thing if your patient woke up blind (hello, malpractice!). 

Auditory Evoked Potential (AEP) are used to monitor the integrity of CN VIII. We didn't use this today but I read that they can be very helpful in procedures such as during resection of acoustic neuromas.

Brain

Electroencephalography (EEG) is the summation and recording of postsynaptic potentials from the pyramidal cells of the cerebral cortex. The EEG is typically classified by frequency (alpha, beta, theta and delta waves). The EEG can be recorded off the scalp and forehead using surface and needle electrodes and reflects the overall metabolic activity of the brain. Why would this be helpful during surgery? Metabolic activity of brain cells requires energy so if there are problems or alterations with energy supply or production (hypoxia or ischemia) the brain cells will affect the readings on the EEG. 

A subset of the EEG that I have been seeing a lot of in all of the surgery rooms (not just neuro) are the Bispectral (BIS) monitors. BIS monitor is a derived EEG parameter used to measure the depth of hypnosis under anesthesia. A number above 80 indicates emergence from anesthesia. A value between 40-80 usually implies adequate hypnosis without possible recall. Recall is something that the anesthesiologist wants to prevent a patient from experiencing as it can be a very traumatic event psychologically. I have sensed from the residents and attendings that BIS is a very "rough" estimate and should not be used to assess blood flow to the cortex but only be used to get a general idea of "consciousness" of the patient. 

That's all for today! This got me even more excited for my Neurology rotation! I only have almost 1 more week left of Anesthesiology! 

Perioperative Management of Blood Glucose

Diabetes is so prevalent that it very common to be managing patients perioperatively with this chronic disorder. I felt that a post was necessary because there are reasons why tight glucose control is important and also multiple methods to managing blood glucose. Studies have shown that there is a decreased morbidity (decreased risk of infection, cardiovascular complications...) with blood glucose control. Blood glucose levels can be difficult to control during surgery and anesthesia, however, due to an increase in counterregulatory hormones (epinephrine, glucagon, cortisol, cytokines and interluekins) which will lead to insulin resistance and decreased peripheral utilization causing hyperglycemia.  Pts are NPO before surgery which can lead to difficulty managing blood glucose levels.  

The goals of perioperative managment in diabetic patients include...

• Avoidance of hypoglycemia (<40 can cause arrythmias or cognitive defects)
• Maintain a balance of electrolytes (hyperosmolar states can causes osmotic diuresis)
• Avoidance of hyperglycemia
• Prevention of ketoacidosis

I checked on uptodate and there are actually no clear optimal guidelines for the glucose range but it was recommended to keep the glucose readings between 140-200. The article stated that trying to get the glucose levels to a normal value was not associated with a reduction of post op infections or cardiac events but was associated with an increase in hypoglycemic episodes.

Strategies to maintain the target ranges for glucose (again, there is no optimal range set as of now) have been proposed and are described below.

Type 2 diabetes treated with diet alone

These patients do not need any therapy perioperatively unless their glucose levels climb out of the target range. If correction is needed, the pt can be treated with rapid-acting (lispro, aspart or glusine) or short-acting (regular). Short surgeries (2 hours or less) can check the blood glucose before and after surgery. Longer than 2 hours, you can check the blood glucose every 1-2 hours intraoperatively.

Type 2 diabetes patient's treated with oral hypoglycemic agents or non-insulin injectables (not insulin)

Pt can continue their normal medication regimen but hold their oral diabetic medication the morning of surgery. If the patient climbs to the out of target range, they can be treated with short or rapid-acting insulin. Pt can restart medication after pt is able to eat with the exception of metformin which can be restarted after the patient has documented adequate renal function. Sulfonylureas have a side effect of hypoglycemia and should only be restarted once it is documented that the pt can eat. Thiazolidinediones should not be used if the patients develop CHF, edema or liver function abnomalities.

Insulin dependent diabetes

If the procedure is not long or complex (transplant, bypass surgery or neurosurgery) the patient can be treated with subcutaneous insulin. For longer, more complex operations, the patient will need IV insulin drip. IV insulin requires close monitoring and should be checked about every hour. The amount of insulin to give in units/hour can be calculated by this helpful algorithim...

Blood glucose/100 = Units/hour
Example- blood glucose = 210              210/100 = 2.1 = 2.1 Units of Insulin/hour should be given

Interesting point came up in surgery today. We had a patient with insulin dependent diabetes and also had a bad history of post-op n/v so we wanted to give her plenty of anti-emetics but we did not give her dexamethasone because of its side effect of hyperglycemia. I read in uptodate though that small doses of dexamethasone, 4-8mg, had a very small hyperglycemic effect. I am unsure if a dose that small would be helpful with anti-emetic action.


I wanted to give myself a little overview of the management but because there are still no optimal guidelines set in place I believe that the management will vary depending on the hospital.

Stroke Etiology, Diagnosis and Management

I am getting excited for my Neurology rotation coming up and I thought it would be a good idea to go over some very basic neurology before I start.

Definition - A stroke is the acute neurologic injury that occurs as a result of ischemia or hemorrhage of the brain.

Ischemic Stroke - 80 % of strokes and include the following causes

• Thrombosis - Essentially, the stenosis of a critical artery (MCA, ACA, internal carotids or PCA). You can divide the etiology into extracranial vs intracranial vessels
• Embolism -  refers to particles of debris originating elsewhere that block arterial access to a particular brain region. Common origins of the debris include emboli from atrial fibrillation and from a DVT in a pt with a PFO or septic emboli
• Systemic hypoperfusion - from a circulatory problem causing decreased perfusion to the brain. Causes include blood disorders (Essential thrombocytopenia, PCV, factor V mutation...)

Hemorrhagic Stroke - 10 % of strokes and include the two main subtypes

• Subarachnoid - most often due to a ruptured aneurysm which bleeds directly into the subarachnoid space and CSF. Risk factors for rupture of aneurysm can be remembered by the mnemonic SHAME (Smoking, HTN, Adult Polycystic Kidney Disease, Marfan's Disease and Ehler's Danlos)
• Intracerebral -  most common causes of ICH are hypertension, trauma, bleeding diatheses, amyloid angiopathy, drug use such as amphetamines and cocaine, and vascular malformations

When a patient comes in with stroke symptoms (facial drop, weakness, slurred speech...) what labs and tests should you be ordering?

• CT of the head w/out contrast is the best initial diagnostic test
• O2 Saturation and treat with supplemental O2 if < 94%
• Blood glucose - hypoglycemia can present similar to stroke and severe hypoglycemia can actually cause neurologic damage. Hyperglycemia can cause neurologic damage as well
• INR - can reverse if pt has a high INR
• EKG - check for atrial fibrillation
• BP readings - if stroke is ischemic don't treat unless it is > 220 systolic and can use labetalol. If the patient is a candidate for tPA therapy, the BP needs to be < 185/110 and can treat with nitroprusside or nicardipine

Treatment - Once you have determined whether the stroke is ischemic or hemorrhagic and the cause, you can treat.  All pts are usually admitted to an ICU or floor with nurses trained in post-stroke managment. 

Ischemic Stroke Treatment

• tPA administration is pt is eligible for administration (within the 3 hour window) and has no contraindications (see note)
• Aspirin or if pt is allergic to aspirin, clopidogrel or dipyridamole
• If the EGK showed new onset afib, pt will need to be on a heparin drip before placed on coumadin.  Side note: If a pt is placed on coumadin without bridge therapy, the pt is at risk for warfarin skin necrosis - induced by a transient hypercoagulable state. The initiation of warfarin at standard doses leads to a decrease in protein C anticoagulant activity because if you remember, protein C will deactivate clotting factor VIII. Skin lesions occur secondary to the throbosis and will be seen on the extremities, breasts, trunk, and penis. If a product containing protein C is not rapidly administered, the affected cutaneous areas become edematous and can ultimately become necrotic.
• Echocardiogram
• Carotid angiogram and endarterectomy is the carotid is > 70% stenosed
• Have lorazepam or diazepam ready because post-stroke seizure can be seen in 1 out of 5 pts post stroke

Hemorrhagic 

• FFP if INR is high
• surgical coiling/clipping
• decreased BP to < 165 with nicardipine (a CCB that will also prevent vasospasm)
• Pt's head should be at a 30 degree incline to decrease intracranial pressure 

Contraindications to tPA

• Recent head trauma or stroke within last 3 mo
• Arterial puncture in a noncompressible vessel within the last 7 days - there may be a clot in place that is preventing that recent arterial puncture from bleeding out so you don't want to lyse that clot in particular
• Acute internal bleeding/trauma
• INR > 1.7
• BP > 185/110
• platelets < 100,000
• glucose < 50
• Any hx of intracranial bleed
• hx of a multilobar infarct

Hyponatremia

Defined as a serum sodium < 135. The first step when working up hyponatremia, is to look and make sure that it is true hyponatremia by calculating the serum osmolality. 

Serum Osmolality = (2 x Na) + (glucose/18) + (BUN/2.8)

If the serum osmolality is < 290, then it is true hyponatremia

If the serum Na is > 290, there is an osmolyte in abundance causing a pseudohyponatremia

Osmolytes that would cause pseudohyponatremia include...

• Hyperglycemia
• Hypertriglyceridemia
• Hyperglobulinemia
• Mannitol

Once you have established the fact that there is true hyponatremia, assess the patient's volume status (BP, orthostatic BP, mucous membranes, I/O, peripheral edema). The causes of hyponatremia can be categorized under euvolemia, hypovolemic or hypervolemic

Euvolemia - all causes measure the urine Na < 20

• Psychogenic Polydipsia
• SIADH - the following criteria
• Serum Na < 135 and serum osmolality < 290
• Euvolemia
• Inappropriate urine osmolality - this is how you would distinguish SIADH from Psycogenic polydipsia
• Adrenal Insufficiency - cortisol has a negative feedback loop on CRH. If there is no cortisol due to adrenal insufficiency, the release of CRH is stimulated and CRH has a positive affect on the release of ADH and ACTH. The ADH will cause reabsorption of water from the kidneys. 
• Hypothyroidism
• Diuretics (TZDs)
• Extasy 
• Low dietary intake of solutes (potomania)

Hypovolemia - losing too much Na

Urine Na > 20 - kidneys are not functioning because they are not reabsorbing Na

• Diuretics
• RTAs
• Urinary obstruction
• Tubular interstial disease

Urine Na < 20 - kidneys are responding appropriately to volume depletion 

• Vomiting 
• Diarrhea
• Burns
• Excessive sweating

Hypervolemia - retaining too much Na (seems counter intuitive but think about the rule wherever Na goes, water follows which will cause a hyponatremia)

Urine Na > 20 - again, means something is wrong with the kidneys

• ESRD - pt will be anuric and will have a urine output of < 100 ml/day

Urine Na < 20 - body thinks that it is hypovolemic because you are third spacing your fluid. This this fluid is not going to the kidneys and the kidneys think that you are hypovolemic so they reabsorb as much fluid as possible

• HF
• Cirrhosis
• Nephrotic Syndrome

Treatment - Divide the categories into if the patient is symptomatic vs asymptomatic

Symptomatic - Happens when the hyponatremia is acute < 48 hours. pt is lethargic, confused, seizures

This is a situation where it is ok to give 3% saline. That can be very dangerous though so my attending told me that he will give about a 500 cc (100 cc brings it up about 1 point of serum Na) bolus of 3% saline and recheck the serum Na in 1-2 hours. The goal of correction is about 4-6 mEq but don't want to correct more than 2 meq/hr. 

Asymtomatic - Hyponatremia is usually chronic  > 48 hours. Treat according to volume status and DON'T give 3% saline. Goal of correction is about 8-12 meq 24 hours

Hypovolemia - Replete the patient with NS

Euvolemia - water restriction 1200-1600 ml/day was what we usually did

Hypervolemia - water restriction, diuretics

Hypokalemia

I got a little excited today when my patient had hypokalemia and the anesthesiologist asked me for a possible differentials. Don't get me wrong, I haven't been bored on Anesthesiology and I am actually enjoying it more than I thought I would. They have been letting me intubate patients which is beneficial for my future career. I just miss running through differentials! The most obvious reason for the patient's hypokalemia was redistribution from her respiratory alkalosis, but unfortunately we can't work up a pt in surgery like we can on the wards. Still, I wanted to revisit this topic today. 

First, check to make sure that the patient is not having any changes on EKG. If the patient is stable, you can go ahead and work up the cause for the hypokalemia. Second, check the metabolic acid base status. 

Normal Metabolic Acid Base

This category includes hypokalemia from redistribution or extrarenal losses. Redistribution occurs when there is an increase in exchange of potassium from extracellular to intracellular space. Redistribution occurs in the following situations...

• Catecholamine excess
• Alkalosis (resp alkalosis in my patient)
• hypokalemic periodic paralysis
• Insulin administration
• Albuterol inhaler or beta 2 agonist
• Barium poisoning

Extrarenal losses include...

• Simply, decreased potassium intake
• Laxative abuse

Metabolic Acidosis

Divide this category into if the urine potassium is < 20 (not a problem with the kidneys) or > 20 (problem with the kidneys). 

Urine potassium < 20 - This tells you that the kidney is doing its job holding onto the potassium and that the losses are extrarenal . These losses include...

• Diarrhea
• Laxative abuse - you can have both a normal or met acidosis with laxative abuse

Urine potassium is > than 20 - This tells you that something is wrong with the kidneys because if your body was experiencing hypokalemia, than the kidneys should be doing their job reabsorbing the potassium to help correct the hypokalemia. Causes include...

• Renal Tubular Acidosis - See other post on RTAs
• Carbonic anhydrase inhibitors
• organic acidosis

Metabolic Alkalosis

Check the urine K and the urine chloride. If the urine K is < 20 think of vomiting as a likely cause. If the urine chloride is > 20, you divide the categories into if the patient has a normal BP or high BP. 

Normal BP

• Bartter's syndrome
• Diuretics

High BP

• Hyperaldosteronism
• Essential HTN with diuretic use
• Hypercortisol
• Mineralcorticoid ingestion (licorice, Liddle's syndrome)

Treatment - Always check the Mg level in the patient as Mg will stabilize the nephron and reduce the urinary loss of K. If the patient is asymptomatic, give potassium supplementation (10 meq roughly will increase the serum K by 0.1 meq/L). The equation used to calculate the potassium deficit is...

(Goal K - Serum K)/Serum Cr x 100 = Total meq of K required

Don't use D5W or fluids with high glucose as glucose will cause an increase in insulin which will further drive K intracellularily and exacerbate the hypokalemia. Most common fluids to use for repletion are KCL, KHCO3 and can also use KPO3 depending on the coexisting deficits. 

Total Intravenous Anesthesia - TIVA

Today, we used TIVA to induce anesthesia on my patient instead of any inhaled anesthetics. TIVA is anesthesia administered entirely by the intravenous route eliminating the use of inhaled anesthetics. TIVA offers several advantages over the traditional volatile anesthetic method (isoflurane and sevoflurane). These advantages include reduced air polution, greater hemodynamic stability, decreased post-op nausea and vomiting and decreased pulmonary vasoconstriction. The reason why we used it on our patient today was that she had problems in the past with severe nausea and vomiting post anesthesia. 

Situations Where TIVA is Useful

• Pts at risk of post op nausea and vomiting
• Neurosurgical procedures
• History of Malignant Hyperthermia
• Bronchoscopy or ENT surgery
• Ambulatory setting
• Lobectomy via thoracotomy or pneumonectomy

Commonly Used Drugs for TIVA

Propofol-This is the only available intravenous hypnotic agent suitable for induction and maintenance of anesthesia. Propofol offers many advantages including rapid recovery of consciousness and psychomotor function and has a lower incidence of post-operative nausea and vomiting.

Remifentanil - This is an ultra short acting opioid. It has been established as the drug of choice for TIVA with propofol (we used this along with propofol today). The resident asked me how remifentanil was metabolized and since it is an opioid, I guessed that it was hepatically metabolized. I was wrong because I didn't think about the fact that it remifentanil is metabolized very rapidly which points more towards an enzyme. So, "some kind of enzyme" was my lame second guess. Remifentanil is metabolized by esterase and thus, it has a very short half life. Because of this, my resident told me that at the end of surgery, BEFORE we turn off the remifentanil drip, we will give a dose of fetanyl which hangs around in the body for a much longer time and will provide analgesia. After we give the fetanyl, we can turn off the remifentanil drip which will ensure that the patient will not be in pain once the remifentanil wears off.

Other medications that can be used include Sufentanil and Alfentanil

Types of Shock and Pressors

While on my Anesthesiology rotation, I notice that we always have different types of pressors handy to control the pt's MAP during surgery. When the patient had a low MAP but a higher HR, we would give the patient phenylephrine because it acts only on the alpha receptors and would therefore, not cause tachycardia. If the patient had a low MAP and a low HR, we would give Levophed (norepinephrine) because it has a side affect of increasing the HR. Choosing the correct pressor reminded me about my ICU rotation way back in the fall and I wanted to brush up on the different types of shock and the medications used to treat. There are four categories of shock: Hypovolemic, cardiogenic, distributive and combined. To help distinguish between the different types, you look at a few different measurements: SVR (systemic vascular resistance meaning the afterload), PCWP (Pulmonary Capillary Wedge Pressure meaning the preload) and CO (cardiac output).

Hypovolemic

Induced when a cause for decreased preload to the heart occurs which causes a decrease in cardiac output. Cardiac output = HR x SV. When you have a decrease in preload, the SV (stroke volume) will go down thus, decreasing the CO. The body reacts to the decreased CO by increasing the SVR to compensate for the diminished perfusion to vital organs. The PCWP will, of course, be low. 

Causes for hypovolemic shock can be divided into 2 categories

1. Hemorrhage-induced – trauma, GI bleed, ruptured hematoma, hemorrhagic pancreatitis, fractures, or a ruptured aneurysm

2. Fluid loss-induced – diarrhea, vomiting, heat stroke, insensible losses such as burns and "third spacing". Third-space losses are common postoperatively and in patients who have intestinal obstruction, pancreatitis, or cirrhosis. 

Treatment - FLUIDS!! There are three classes of fluids: crystalloids, colloids and blood products. If the patient is in hypovolemic shock secondary to blood loss, you will obviously give PRBCs. Crystalloids are usually used before colloids as they are less expensive and effective. 

Cardiogenic

Cardiogenic shock occurs when there is cardiac pump failure.When the cardiac pump fails the CO decreases and again, the SVR increases in an effort to compensate for the diminished perfusion to the vital organs. This looks very similar to hypovolemic shock except in this case the PCWP is increased because there is plenty of fluid but it is stopping up in the heart causing an increase in pressure in the pulmonary artery. 

Causes can be divided into 4 categories: myopathic, arrhythmic, mechanical, or extracardiac

Cardiomyopathies- In a sum, all of these causes are due to pathology of the cardiac muscle severe enough to affect the pumping ability of the heart. Severe MIs, dilated cardiomyopathies, stunned myocardium following prolonged ischemia or cardiopulmonary bypass and myocarditis

Arrhythmias - Both atrial and ventricular arrhythmias can produce cardiogenic shock. When the atrium are not contracting correctly, there will be improper filling of the ventricles and therefore a decreased CO. If the ventricles are not contracting correctly, then there will be a poor stroke volume which will also decrease the CO. Ventricular fibrillation will completely abolish CO while other arrythmias of the ventricles will decrease the CO. 

Mechanical - Causes include valvular defects, ventricular septal defects or rupture, atrial myxomas, and a ruptured ventricular free wall aneurysm. An atrial myxoma can reduce ventricular filling by obstructing the flow of blood. A ruptured left ventricular free wall aneurysm can produce pump failure as well.

Extracardiac – Extracardiac (obstructive) causes of cardiogenic shock include anything that would cause strain on the heart and decrease cardiac output such as a pulmonary embolism, tension pneumothorax, severe constrictive pericarditis and tamponade.

Treamtent - I am not going to go into detail here. You could guess what the treatment may be for many of these (fix the underlying problem). I do want to talk about pressors and what type would be appropriate for cardiogenic shock. 

Dobutamine - has a greater action on B1 than B2. Acting on the B1 receptors will improve cardiac output by increasing pumping function of the heart. 

Norephinephrine - acts on alpha and beta 1 receptors but alpha action is > than beta. Will vasoconstrict and improve pumping function of the heart. 

Epinephrine - also acts on alpha and beta receptors but when compared to norepinephrine, alpha action = beta action. Thus, it improves cardiac contractility even more than norepinephrine.

Phosphodiesterase Inhibitors - will cause vasoconstriction

Distributive

Distributive (aka vasodilatory) shock is a consequence of severely decreased SVR (will see hypotension). In this type of shock, the cardiac output is increased (will see tachycardia) to compensate for the decreased SVR. Pt's skin will feel warm due to the decreased SVR.

Causes - anything that will cause vasodilation of the blood vessels such as sepsis, toxic shock syndrome, SIRS, Addison's crisis, drug toxins and anaphylaxis.

Treatment - the main problem here is systemic vasodilation. You will want to have a pressor that acts strongly on the alpha receptors. You can use epinephrine, norepinephrine or phenylephrine. 

Combination

Any of the above types of shocks can coexsist. I recall a pt I had in the ICU who had sepsis as well as necrotizing pancreatitis so he had a combination of hypovolemic shock and distributive shock. 

Fluid management during Surgery

Anesthesiologists have a lot of control in how much fluid a patient will be given during a procedure. I remember coming across the equation for maintenance fluid (4-2-1 rule) for my surgery shelf exam but have long since forgotten it. I wanted to remind myself here about the process of figuring out the amount of fluid a patient should be given during a procedure. 

1. Take the patient's weight in kg

2. Multiple the 1st 10 kg by 4

3. Multiple the 2nd 10 kg by 2

4. Multiple the leftover kg by 1

5. Add them all up and you will get the maintenance fluid in mL/hr

Example

1. Pt weighs 88 kg 

2. 4 x 10kg = 40

3. 2 x 10kg = 20

4. 1 x 68kg = 68

5. 40 +20 + 68 = 128 mL/hr

When your patient is going to have surgery, they usually have been NPO for 7-12 hours. Once you have the maintenance fluid amount, you can figure out what the patient's deficit is. So, if my patient in the example has been NPO for 10 hours, then I would multiple 128 mL x 10 and say that they have a 1.28 L deficit. 

Another factor that you need to think about is fluid loss during the procedure which includes blood and evaporation. This is called insensible loss. Loss due to evaporation is case dependent (3-15 cc/hour). You will have more evaporation loss in an open case versus a laparoscopic case. Blood loss to crystalloid ratio should be replaced in a 1:3 ratio. So, if my patient lost 300 cc of blood during the procedure then I would add on 900 cc of NS to the fluid total to be given. 

Hypernatremia

This was another common reason for consultation on my Nephrology rotation. Hypernatremia is defined as the serum Na > 145. Before I would see the patient, I would read up on their history and hospital/ED course and ask myself what type of fluid loss or fluid gain most likely occurred? Was it pure free water or did the patient lose sodium and potassium with it? Is the pt receiving TPN? Hypernatremia causes can be divided into 3 main categories and the treatment changes depending on the cause and type of fluid lost. 

1. Water Loss into the Cells

This is the least common cause. Water can momentarily move intracellularily causing a relative extracellular hypernatremia. This can occur after severe exercise of post electroshock induced seizures. 

2. Free Water Loss

This is the most common cause. You can lose free water through the skin, GI tract or urine.

Skin-when you sweat, you lose free water because the sweat glands reabsorb the sodium. 

GI-vomiting and gastric suction removes hypoosmolar fluid. Fluid replacement with gastric suction was a common mistake that I would see on the wards. A pt who had a bowel obstruction would have an NG tube placed. At the same time, the patient was NPO so they would be on IV fluids. The IV fluids would be NS and as a result, the patient would start to trend towards hypernatremia because the fluid that was being removed from the NG tube was hypoosmolar. Diarrhea can cause hypernatremia if it is secondary only to osmotic causes and not secretory causes where you are losing both free water and solutes (VIPOMA and cholera). Osmotic causes of diarrhea include lactulose, charcoal and bacterial. 

Urine-free water loss can occur in the urine if it is secondary to osmotic causes. This can occur in DKA when there is so much glucose being spilled into the urine that osmosis will cause free water loss into the urine to dilute it (This was the most often reason for hypernatremia on my rotation). Other causes of osmotic diuresis would be mannitol administration or if the patient had a prolonged period of azotemia that had resolved and the kidneys were filtering out the excess urea. 

3. Sodium Overload

This could occur several different ways. One cause is iatrogenic causes. Imagine the situations in the free water loss category. Iatrogenic sodium overload could occur when there was free water loss but the patient received NS as fluid replacement. Salt poisoning is another cause and can be manifest in the form of child abuse. FENA will show a Na excretion of > 2% because the kidneys are trying to rid the body of excess Na. A third cause of sodium overload is if the pt is receiving TPN and tube feeds which are hypertonic in solutes. 

Treatment

There are four steps to determining the best treatment. If free water was lost, you will want to give D5W because 2/3 of this fluid will move into the intracellular space which is where you want it to go. If the patient has hypernatremia due to free water loss but has a little bit of vascular depletion as well, then you will want to add a bit of NS to the bag (NS will go to the vascular space and is used for volume repletion). A few of our patients were in this situation so, we gave them D5W1/4 NS. 

First, determine the free water deficit with the following equation

TBW in kg x 0.5(women) or 0.6 (men) x (serum Na/140-1)

Second, determine the appropriate rate of sodium correction. For acute hypernatremia (occurs < 48 hours) the serum Na should be lowered to normal levels within 24 hours. You can use D5W 3-6 mL/kg/hr and monitor the Na level every 1-2 hours until the Na is < 145. For chronic hypernatremia, you want to replace about 10 mEq/24 hours. Give D5W 1.35 mL/hour/kg. 

Third, you design a fluid replacement regimen. 

For acute hypernatremia, you want to replace the entire fluid deficit within 24 hours. 

For chronic hypernatremia, you want to replace the half of the fluid deficit within 24 hours

Fourth, calculate the ongoing fluid loss that occurs every day and add that to the fluid amount. The equation is 

Urine volume output/hour x ((UNa + UK)/serum Na)

Renal Tubular Acidosis

My Nephrology attending told me that even though RTA's are not very common in the population, they are a favorite topic on the boards. 

Type 1 Distal RTA

Pathology-a defective H/K pump in the distal tubule. As a result, the kidneys fail to secrete hydrogen into the urine and they fail to reabsorb potassium back into the lumen.

Clinical Presentation-Since the kidneys are unable to secrete hydrogen into the urine, there will be acidemia of the blood and the urine will be alkaline pH > 5.4. Since the kidneys cannot reabsorb potassium from the urine, there will be hypokalemia. Nephroliathasis can be a problem because stones will form in more alkaline urine and acidemia of the blood will cause bone resorption. 

Causes-Think autoimmune disorders (Sjogren’s, RA, SLE). Drugs (ifosfamide, ampho B, lithium), sickle cell anemia, hypercalciuria, hyperglobulinemia, cirrhosis, obstructive uropathy, or renal transplant.

Diagnosis-Acid load the body with ammonium chloride. Even though you have put acid in the body, the urine will remain alkaline because the kidneys cannot excrete the excess hydrogen. There will be a positive urine ion gap. A positive urine ion gap can happen 1 of 2 ways. 

UAG = (Na+K) - (CL) = Unmeasured anions-Unmeasured cations

1. If the Unmeasured cations are = 0 then you will get a positive UAG. NH4+ is the form of acid that the kidney secretes. If it is unable to secrete the acid, as is the case in RTA type 1, then you will be a 0 for the unmeasured cation and thus, a positive UAG. 

2. If the Unmeasured urine anion is extremely elevated 

Treatment-Oral Bicarbonate. This will treat the acidemia and also help prevent nephrolithiasis by making the urine more alkaline. 

Type 2 Proximal RTA

Pathology-The kidneys have defective HCO3 reabsorption. 

Clinical Presentation-The urinary pH will be <5.4. When I was revisiting this, I wondered why the urine wouldn't be alkaline if the kidneys were unable to reabsorb bicarbonate. The reason is that the defect is in the proximal part of the tubule. The distal part of the tubule still works well so the kidneys are able to acidify the urine and will correct the acid base balance in the end. There will also be hypokalemia because the early acidemia of the urine will cause overactivation of the H/K pumps and will secrete out more K into the urine. RTA type 2 may also cause rickets or osteomalacia. This is because a defect in the proximal tubule causes loss of phosphate into the urine. 

Causes- In adults think multiple myeloma or certain drugs. The light chains in multiple myeloma are resistant to degradation in the proximal tubular cells and accumulate there to cause impairment. Other things to consider are primary causes such as familial disorders (cystinosis, Wilson’s, glycogen storage disease type I. Secondary causes include multiple myeloma, amyloidosis, drugs (ifosfamide, carbonic anhydrase inhibitors), heavy metals (lead, mercury, copper). It helps me to remember this by thinking about the heavy metals getting flushed into the renal tubules and damaging the first part that they come into contact with which is the proximal tubule.  

Note-Fanconi's Syndrome is a disorder of the proximal tubule and but more generalized than RTA type 2 defect of diminished HCO3 reabsorption. In Fanconi's syndrome, the kidneys lose almost everything that is suppose to be reabsorbed in the proximal tubule so you will see glucosuria, phosphaturia, uricosuria, aminoaciduria, and tubular proteinuria. Most Fanconi's syndrome cases will include a type 2 RTA. 

Diagnosis-measure HCO3 in the urine

Treatment-Thiazides, oral bicarbonate and vitamin D supplements may be needed to treat underlying bone disease. 

Type 4 RTA AKA Hyperkalemic RTA

Pathology-cause is that the kidneys have a generalized transport abnormality of the distal tubule. This form is distinguished from classical distal RTA and proximal RTA because it results in high levels of potassium in the blood instead of low levels. It can occur when blood levels of the hormone aldosterone are low or when the kidneys do not respond to Aldosterone. Aldosterone directs the kidneys to reabsorb Na and excrete K. 

Clinical Presentation-Hyperkalemia and symptoms such as low BP, salt craving or DM

Causes-Due to either aldosterone deficiency (diabetic nephropathy) or tubular resistance to the action of aldosterone (chronic tubulointersitial disease or potassium-sparing diuretics). 

Diagnosis-Low serum aldosterone 

Treatment-Furosemide, mineralcorticoid replacement such as Fludrocortisone. 

Evaluation of Acute Kidney Injury

Along with hyponatremia, acute kidney injury was one of the most common reasons for consultation on my rotation. To diagnose acute kidney injury, you need one out of the following three criteria

• An increase in serum creatinine of ≥0.3 mg/dL (≥26.5 micromol/L) within 48 hours
• An increase in serum creatinine of ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days; or
• Urine volume <0.5 mL/kg per hour for more than six hours

Before I would go and see the patient, I would look through their chart and ask myself the following questions

• What is the patient's baseline creatinine? (is this acute kidney injury of acute on chronic kidney injury?)
• Has the patient received any IV contrast? 
• Have they been on any antibiotics as an outpatient or inpatient that are nephrotoxic (aminoglycosides, sulfonamides...)
• Has the patient been on any medications that could cause acute kidney injury? (NSAIDS, ACEi, diuretics, chemotherapy agents, antivirals or immunosuppressants)
• Does the patient have anything in their history that would decrease renal blood flow? (diarrhea, vomiting, decreased oral intake, sepsis, hypotensive episodes charted on vitals, third spacing of fluids)
• Any reason to suspect obstruction to urine outflow? (BPH, hx of uterine cancer, nephrostomy tubes or ureter stents)

Once I would gather the history from the chart, I would go see the patient and do a thorough H and P. I would try to assess their volume status by examining the following

• Mucous membranes moist or dry?
• Skin turgor?
• Evidence of poor perfusion? 
• Any evidence of fluid overload on exam? (JVD, ascites or edema)
• I/Os

Gathering the data above would usually give me a give me a high suspicion of the etiology of the patient's renal failure. Acute kidney injury causes can be divided into three categories: Pre-renal, Intrinsic and Post-renal

Pre-Renal Failure-This is the most common cause of acute kidney injury. A decrease in mean arterial blood pressure will cause an increase in sympathetic tone which leads to increase in renin which leads to vasoconstriction of the efferent arterioles causing a decrease in renal perfusion and thus an increase in creatinine. Causes for pre-renal failure include...

• True volume depletion-GI (vomiting, diarrhea, bleeding), Renal losses (diuretics, osmotic agents), loss through skin (sweating and burns) and third space sequestration (crush injury and skeletal fracture)
• Edematous states-Heart failure, cirrhosis and nephrotic syndrome
• Selective renal ischemia-Renal artery stenosis made worse by treatment with ACE inhibitors, Ang II blockers
• Drugs that affect the glomerular hemodynamics-decrease the arteriole dilation (NSAIDs decrease prostaglandins) or that increase efferent constriction (ACEi or Arbs which cause vasoconstriction of the efferent arteriole) 

Intrinsic Renal Failure-Etiology is damage to the renal parenchyma (intrinsic renal injury) and Acute Tubular Necrosis is the most common cause of intrinsic renal failure so I will focus on ATN and the three major causes of ATN.

• Severe renal ischemia-severe hypotension, thombotic event
• Sepsis-again, it is due to decreased perfusion but you also get an increase in cytokines and activation of neutrophils which cause inflammation of the renal tissue
• Nephrotoxic agents administered

Post-Renal Failure-when there is a long term obstruction to urine flow, the urine will back up through the ureters and can cause hydronephrosis. There is a point where the damage to the kidneys is so severe that it is not reversible.

• Obstruction within the urinary system-stones, blood clots
• Obstruction outside the urinary system-Enlarged prostate, strictures, retroperitoneal fibrosis or tumors

So, again the hx and physical will more than likely point you in one of these directions but there are a few lab test and treatment that you can do to help with the etiology. 

• UA-Examine the sediment. Are there any type of casts? Eosinophils present?
• FENA- looks at urine lytes and intact kidney function. <1% is more consistent with prerenal failure and >1% more consistent with intrinsic and post renal failure. 
• Response to fluid repletion-This is the gold standard for the distinction between pre-renal and ATN. With fluid repletion, the return of creatinine to baseline within 24-72 hours is consistent with pre-renal failure. The only exception to this is pre-renal failure secondary to edematous states. These patients are fluid overloaded but need to mobilize the fluid back into the intravascular space.
• Post-void bladder scan and renal US-If a pt has >200 cc of fluid after voiding, they have urinary retention which is more consistent with post-renal failure. A look at the kidneys with an US can tell you if there is any hydronephrosis present which would also point you towards post-renal failure. 

More Notes from Anesthesiology...

I don't have the time or energy to tackle a large subject today but I will write down some information I was given that I think is important. 

On my first day, I learned about induction medications and the emergence process. I wrote that we induced all of my patients with Propofol. Today, we induced both of my pt's with Etomidate. I realized quickly that I knew what the induction medications were but I didn't know the reasoning behind choosing your anesthetic. 

Etomidate-This anesthetic has minimal depression of cardiovascular and pulmonary function.  Ideal for patients with coronary vascular disease, COPD or hemodynamic instablility. Both of my patients today had COPD and were receiving stent placements for aortic aneurysms. An interesting side effect of etomidate is adrenal suppression. I recall that we gave the patient a dose of steroids during the procedure today but I decided that the reason for this was because the patient was on steroids chronically for pain. Now that I am reading up on the medication, I am curious if we gave it in case the patient's adrenal glands were being suppressed. I will need to ask tomorrow. UPDATE: I asked and my attending said that although that it a side effect of Etomidate, it is not routine to give steroids in case there is adrenal gland suppression. 

The resident asked me about why we could not give Lactated Ringers through the warm IV. I tried my best to reason through and come up with an answer but failed miserably! I knew that you would run blood products through the warm IV but I couldn't think of why you wouldn't want to run Lactated Ringers through (contain Na, K, Cl, Lactate and Ca) along with the blood products. The reason is that PRBCs have citrate which chelates calcium. The citrate in the the PRBC could chelate the Ca in the Lactated Ringer solution and could cause a clot and ruin your IV. My resident also told me that there is a very small chance of this happening but a rule that they follow nonetheless. 

I was also reminded of the Mallampati score today as we saw our patients in preop and asked them to open their mouths and stick out their tongue. It helps give a quick assessment of how difficult your intubation may be. 

You give a patient a score depending on what structures you can see when they open their mouth and stick out their tongue. In a class one you can see the hard palate, soft palate, uvula and the pillars. Class two you can visualize the palate, portion of uvula and pillars. Class three you can visualize the soft palate and the base of uvula. Class four you can visualize the hard palate only. 

That's it for today! I am almost done with my first week of Anesthesiology! So far, I have been able to intubate a patient and help start a central line. 

Anesthesia Induction and Emergence Medications

It was my first real day on Anesthesiology. The hours are a little longer than my last rotation, so I am unsure if I will be able to post every day. I learned a lot today but what I really want to retain in my brain is the the procedure of and anesthetic agents used for induction and emergence.  

Anesthesia Induction 

The first part of induction of anesthesia should be pre-oxygenation with 100% oxygen delivered via a face mask. I placed the face mask on my patient and told them to take deep breaths in and out for about 1 min. We watched the pt's O2 sats climb up to 100% and then prepared to intubate the patient. The purpose of the pre-oxygenation step is to maximize the amount of time that can pass after a patient has been anesthetized and before a proper airway is secured because pts may become apneic once they are anesthetized. 

Before you intubate the pt, you need to anesthetize. The most common choices used for IV induction in order of frequency are Propofol, Thiopental, Etomidate, and Ketamine. We used propofol in all of my cases today. How do you know if the patient is properly anesthetized? We check the corneal reflex (CN V1 afferent and CN VII efferent). If the patient didn't have the corneal reflex, we knew that they were properly anesthetized and that we could proceed with the paralytic agent. 

To induced paralysis, administer a neuromuscular blocking agent such as succinylcholine (depolarizing agent) or vecuronium (non depolarizing agent). A twitch monitor is usually used to assess the depth of relaxation, and when the twitch has sufficiently diminished, intubation can be attempted. The resident told me that you will normally have four twitches. 3 twitches mean that 75-80% of the NMJ is blocked, 2 twitches means that 80-85% is blocked, 1 twitch means that 90-95% is blocked and 0 twitches is 100% blocked. I got varying answers on this question, but all of the residents I asked said they like to keep the twitches down to 1-2 and others wanted no twitches at all before they intubated. 

Once the pt is properly paralyzed, you are ready to intubate! I won't write the steps down since it is somewhat technical but I will say that my attending told me that you usually advance (sound?) the tube about 20-22 cm. 

Emergence

The patient's neuromuscular blockade may have slighlty/completely worn off during the procedure or not at all. Acetylcholinesterase inhibitors (neostigmine is the most commonly used) are used to reverse the effects of the blocking agents. They allow more acetylcholine to be available to overcome the neuromuscular blocker effect, but also causing muscarinic stimulation (because, remember that the muscarinic receptors use acetycholine as well). When the muscarinic receptors are activated, the pt will get side effects: bradycardia, diarrhea, lacrimation, salivation and bronchospasm. Thus, you need to administer an antimuscarinic agent as well such as Atropine or Glycopyrrolate (does not cross the BBB) to prevent these unwanted side effects. We used Glycopyrrolate in all of my patients today because it does not cross the BBB and thus, it will not cause as much drowsiness as Atropine. 

Not my most organized post thus far. It was more of a frantic brain dump of information but it will have to do because my day now starts at 4am! Here is to tomorrow and maybe I will get to intubate by myself!

Types of Catheters for Dialysis

Non-tunneled catheters

Designed for short term access and immediate need for access such as acute kidney injury, thrombosed hemodialysis access or poisoning. 

If the pt may need temporary access but for a longer period of time (1-2 weeks) you may use a non-tunneled cuffed catheter. This would be a pt who needs dialysis (has chronic kidney disease) but has not had permanent access placed or an AV fistula has not matured. 

Many different non-tunneled catheters are available (polyethylene, polyvinyl chloride and silicone). The catheter has a cone shaped tip. It will be rigid at room temperature but will soften at the body's internal temperature. Non-tunneled catheters are usually short (9-20 cm) to avoid the catheter from entering the right atrium of the heart. 

Infections are always a risk with catheters and the risk increases with the time a catheter is in place. The duration of time that a non-tunneled catheter can be in place varies depending on the placement. Non-tunneled catheters placed in the Internal Jugular vein and Subclavian vein can remain in place for 2-3 weeks safely. Femoral catheters, however, are only safe for either one dialysis session or 3-7 days in a bed bound patient. 

There is a higher risk of a pneumothorax when placing a catheter in the subclavian vein than in the internal jugular vein. 

Tunneled Catheters

Tunneled catheters are primarily used for intermediate or long-term (>2 weeks). Although chronic hemodialysis using arteriovenous access is preferred, some pts are poor candidates. In the following situations, prolonged use of tunneled catheters are appropropriate.

-A bridge while awaiting AV access

-Pt has unsuitable vascular anatomy

-AV access may place increase the pt's risk for complications (high output cardiac failure, myocardial ischemic events or steal syndrome-pain or numbness in the hand indicated decreased blood flow)

Tunneled catheters generally have a polyester cuff that is tunneled under the skin from about 3-8 cm. This tunnel is thought to allow tissue ingrowth that will seal off the catheter. This is thought to decrease the risk of infection. Tunneled catheters have a larger lumen as well and allow for higher blood flow than the non-tunneled variety. 

The duration of time that a tunneled catheter can be in place is variable. With proper care the tunneled catheter may remain in place for 1-2 years. 

Arteriovenous Access 

This is the preferred access for chronic hemodialysis. When compared with tunneled catheters, AV access has a lower rate on infection/bacteremia, decreases rate of hospitalizations, increased events of adequate dialysis and a decreases risk of death. There are two main types: arteriovenous fistula and arteriovenous graft. 

Arteriovenous fistula-a type arteriovenous access. An AV fistula is created by connecting an artery directly to a vein, most often in the forearm. Connecting the artery to the vein causes more blood to flow into the vein which causes the vein grows larger and stronger, making repeated needle insertions for hemodialysis treatments easier. 

An AV fistula requires advance planning because a fistula takes a while after surgery to develop (4-24 months). But a properly formed fistula is less likely than other kinds of vascular access to form clots or become infected. Also, properly formed fistulas tend to last many years—longer than any other kind of vascular access. 

How do you know when it is mature? My attending told me that you will be able to easily visualize a prominant vein up the forearm, hear a bruit and there will be a palpable thrill. 

Arteriovenous graft-If you have small veins that won’t develop properly into a fistula, you can get a vascular access that connects an artery to a vein using a synthetic tube, or graft, implanted under the skin in your arm. The graft becomes an artificial vein that can be used repeatedly for needle placement and blood access during hemodialysis. Since you are placing a graft, it doesn't need to mature like a fistula does and can be used fairly soon after placement, often within 2 or 3 weeks.

Compared with properly formed fistulas, grafts tend to have more problems with clotting and infection and need replacement sooner. However, a well-cared-for graft can last several years.

I am leaving out many details but this was a brief overview to help this non-surgically oriented medical student (Internal Medicine, woohoo!) with some basics. 

Hyperventilation Syndrome

02/07/2014

An 18 yo male with a past medical history sig for Anxiety, Depression and OCD presented to the ED on 02/07 with a chief complaint of "my heart is racing and I feel as if I can't catch my breath". Pt stated that he had recently been discharged from West Penn inpatient psych 2 days ago. He was admitted for anxiety attacks, made progress and was doing well until he had been d/c home. For the past day he has been experiencing palpitations and a sense of impending doom. EKG showed tachycardia at 140 bpm and normal sinus rythm with no changes in ST waves, blood pressure was 98/82, tachypnea at 24, Tox screen was negative, CBC normal and CMP showed hypokalemia at 2.3 and hypophosphatemia at 1.5 and low bicarb at 18. Calcium and Mg were nomal. Pt had no other medical problems, was recently started on Abilify, Vistril 2 weeks ago and Ativan prn. He denies smoking, drinking or drugs, glue/paint sniffing. He hasn't had any nausea or vomiting but has had 2 lose bowel movements since yesterday. Physical exam was remarkable for tachycardia only. We, Nephrology, were consulted for the pt's hypokalemia and hypophosphatemia. 

My attending sent me to start the consult. This was a humbling case and reminded me of how little I still know (that happens every day, actually). I was heading down the path of problems with the kidney function itself or possibly a side effect of the new medications (Abilify has a very small, < 1%, side effect of hypokalemia)."The pt has low bicarb and hypokalemia... perhaps he has aquired Renal Tubular Acidosis type II". I wanted lab work that looked at the kidney's ability to function normally such as urine ph and urine lytes. My attending agreed and we went to see the pt together. While in the room, the attending noted that pt took a few deep sighs/min. The pt also told the attending that he has been experiencing numbness and tingling around the mouth and and his thumbs would tighten up. This is where I went wrong. I didn't notice the sighing when I interviewed the pt and he didn't tell me about the tingling or carpal spasms, but I didn't think to ask about them either. My attending was suspicious that respiratory alkalosis may be the cause for his electrolyte abnomalities and ordered an ABG. ABG came back with a PH of 7.52, CO2 of 25 and HCO3 of 17. I learned that this pt's electrolyte abnormalities were caused by Hyperventilation Syndrome most likely secondary to Anxiety. 

Hyperventilation Syndrome

Etiology

Psychopatholgy-The association between hyperventilation syndrome and psychological pathologies (such as panic/anxiety disorder) is strong and the most likely the cause of our pt's hyperventilation and subsequent electrolyte disturbance. As I looked back in the ED records, he had been admitted 1 year ago due to a biking accident with no record of depression or anxiety. At that visit, he had normal electrolytes which makes a disorder of the kidney less likely the cause of his low potassium and phosphate. 

Regulatory systems-Abnormalities in the reticular activating system have been proposed as a cause for hyperventilation syndrome. When asked to breath through a mouthpiece, pt's with abnormal control can have induced hyperventilation and may point to overactivation of the reticular activating system. 

Epidemiology

Up to Date reports that there is a strong correlation with hyperventilation syndrome and anxiety/panic attacks. The prevalence of hyperventilation syndrome has been reported to range from 25 to 83 percent in patients with an anxiety disorder but only about 11 percent in patients with nonpsychiatric medical comorbidities. 

Clinical Presentation

Up to Date states that the cardinal feature of hyperventilation syndrome is a transient increase in minute ventilation. Patients with hyperventilation syndrome present with a variety of somatic and nonsomatic complaints related to the increased respiration.

Somatic signs and symptoms 

Dyspnea-pt complained of this

Light-headedness

Paresthesias-pt complained of perioral parathesisas

Chest pain

Palpitations-pt complained of this

Diaphoresis

Carpopedal spasm-pt complained of carpal spasms

Diagnosis

There is no gold standard and is based mostly on clinical suspicion. Of course, you need to r/o serious underlying causes of hyperventilation (get chest xray and EKG)

Treatment

If psych is the underlying cause, the treatment is based on reassurance, pt education and cognitive-behavioral therapy. Prevention of further anxiety and panic attacks is key. 

So, the patient had Hyperventilation Syndrome but why did he have the electrolyte abnomalities (hypophosphatemia, hypokalemia and decreased HCO3)?

Hypophosphatemia-CO2 is the biggest source of acid in the body because it binds H20 in the blood and forms carbonic acid which then dissociates into H+ and HCO3-.When you hyperventilate, you blow off more CO2 and become alkalotic. Since CO2 diffuses freely across cells, the intracellular PH easily becomes alkalotic. Alkalosis stimulates an enzyme phosphofructokinase which then stimulates glycolysis. Glycolysis increases the formation of phosphorylated carbohydrate compounds in the liver and skeletal muscle. The source of the phosphate needed is in the serum. Thus, you use up serum phosphate and you will see a drop in serum phosphate = Hypophosphatemia!!!

Hypokalemia-In the presence of alkalemia, hydrogen leaves the intracellular space into the extracellular space to try and help achieve a normal PH. Potassium must enter the cell in exchange for the hydrogen leaving the cell to maintain electroneutrality. Thus, you see a drop in drop in serum potassium. 

Decreased HCO3-this is simply the metabolic compensation for the respiratory alkalosis. 

Great case!! I learned a lot with this one!

Disclaimer and first post!

Disclaimer-This is not a blog about my life exactly. I decided to make this blog to help organize my medical encounters and the material that I study. It happens all too frequently that I come home from the hospital with my mind full of medical gems that my attendings handed out and then subsequently lose them because I didn't spend time documenting, thinking etc. It happens even more often that I had a patient with a condition I was uncomfortable working up or treating, but then I forgot to read about it at the end of the day. It is my hope that this blog will end this frustrating cycle. I have tried multiple modalities, but they have been in vain. I thought that since there is a small chance someone may find my postings, I would try harder to be more disciplined and concise with my medical thoughts and patient documentations. If I can try to write about one new topic a day (not quite an attainable goal), I will be more than satisfied with my continuing education. Now, on to my first post!


I just finished a very educationally rewarding rotation in Nephrology and I do not want to lose the ground I have gained. Nephrology is, in my opinion, a challenging field. I encountered on this rotation many topics that I will need to know well to be a good IM intern (electrolyte disturbances, acidosis, alkalosis, acute kidney injury and chronic kidney disease) as well as some uncommon pathology that the Nephrologist will most likely manage.

02/05/2014

Briefly, a 35 yo female with no sig past medical hx  and on no medications came in for an office visit after her urinalysis showed that she had proteinura > 4,028 mg. Labs were negative for secondary causes of nephropathy (ANA, anti-dsDNA, Hepatitis panel, SPEP, UPEP, HIV, ANCAS). Pt's only complaint was mild, generalized swelling in lower legs. Kidney Biopsy was performed and showed fusion of the podocytes on EM. Light microscopy and Immunofluorescence were completely normal. 

                            

Minimal Change Disease

Pathology-Simply, the disruption of the negatively charged membrane in the glomerulus allows increased permeability to anions (proteins!!) which then spill out in the urine thus causing proteinuria. Disruption of the podocytes will compromise the membrane permeability.  

 

Epidemiology-It is the most common cause of Nephrotic Syndrome in children and the cause of primary nephropathy 10-20% of the time in adults. 30% of patients will see resolution of the disease with or without treatment. The rest will have relapsing/remitting cases. 

Causes-Mostly Idiopathic and was the case with our patient. It may be secondary to NSAID use, leukemia, thymoma, malignancy of the kidney, pancreas or duodenum and Hodgkin's lymphoma. 

Diagnosis-Need a kidney biopsy. The Immunofluorescence and Light Microscopy will be normal but you will see effacement, fusion or flattening of the podocytes on Electron Microscopy (our pt had fusion).

Clinical Course-pt will present with sudden proteinuria and may have edema (our pt was complaining of lower leg swelling). You may see acute kidney injury in pts with previously compromised kidneys (atherosclerosis). It is uncommon for the patient to progress to uncontrolled hypertension or end stage renal disease. 

Treatment-Steroids are the cornerstone of therapy as well as reducing the blood pressure in the glomerulus. You treat with 60mg of Prednisone every other day for 4 weeks. Then taper down to 40mg every other day for 4 weeks. About 10 % of patients don't respond to steroid treatment and then you progress to cytotoxic drugs such as cyclosporin, mycophenolate etc. Decreasing the blood pressure with an ACE inhibitor or and ARB is a common addition to therapy. In our case, the patient's repeat UA showed an improvement of the proteinuria and we had her on an ACE inhibitor, lisinopril. After weighing the pros and cons of starting steroid therapy, she decided to wait to and see if her proteinuria continued to improve. She would follow up in 3 months and call if she was noticing any worsening of symptoms (rapid weight gain from swelling, high blood pressure readings). 

Up until now, I had thought that I would probably not see a case of Minimal Change since it was more common in Pediatrics. Surprise!