Analysis & disposition: Monitor kidney indicators in monthly blood tests – Creatinine and BUN had been normal in earlier uses of MTX with bisphosphonates.

Patients undergoing methotrexate therapy should be closely monitored so that toxic effects are detected promptly. Baseline assessment should include a complete blood count with differential and platelet counts, hepatic enzymes, renal function tests, and a chest X-ray. During therapy of rheumatoid arthritis and psoriasis, monitoring of these parameters is recommended: hematology at least monthly, renal function and liver function every 1 to 2 months. More frequent monitoring is usually indicated during antineoplastic therapy. During initial or changing doses, or during periods of increased risk of elevated methotrexate blood levels (eg, dehydration), more frequent monitoring may also be indicated.

(Observation: Pearl wasn’t prescribed any special monitoring tests prior to or while taking methotrexate during any of the three periods she was on methotrexate. The typical monthly tests done were CBC, CMP, C-rP and sed rate).

Transient liver function test abnormalities are observed frequently after methotrexate administration and are usually not cause for modification of methotrexate therapy. Persistent liver function test abnormalities, and/or depression of serum albumin may be indicators of serious liver toxicity and require evaluation.

A relationship between abnormal liver function tests and fibrosis or cirrhosis of the liver has not been established for patients with psoriasis. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the rheumatoid arthritis population.

Pulmonary function tests may be useful if methotrexate-induced lung disease is suspected, especially if baseline measurements are available.

Pancreatitis is an inflammation of the pancreas. The pancreas is a large gland behind the stomach and close to the duodenum. The duodenum is the upper part of the small intestine. The pancreas secretes digestive enzymes into the small intestine through a tube called the pancreatic duct. These enzymes help digest fats, proteins, and carbohydrates in food. The pancreas also releases the hormones insulin and glucagon into the bloodstream. These hormones help the body use the glucose it takes from food for energy.

Normally, digestive enzymes do not become active until they reach the small intestine, where they begin digesting food. But if these enzymes become active inside the pancreas, they start "digesting" the pancreas itself.

Some people have more than one attack and recover completely after each, but acute pancreatitis can be a severe, life–threatening illness with many complications. About 80,000 cases occur in the United States each year; some 20 percent of them are severe. Acute pancreatitis occurs more often in men than women.

Acute pancreatitis is usually caused by gallstones or by drinking too much alcohol, but these aren't the only causes. If alcohol use and gallstones are ruled out, other possible causes of pancreatitis should be carefully examined so that appropriate treatment—if available—can begin.

(Note: Pearl didn’t drink alcohol and gall bladder had been removed 18 years earlier)

Acute pancreatitis usually begins with pain in the upper abdomen that may last for a few days. The pain may be severe and may become constant—just in the abdomen—or it may reach to the back and other areas. It may be sudden and intense or begin as a mild pain that gets worse when food is eaten. Someone with acute pancreatitis often looks and feels very sick. Other symptoms may include

* swollen and tender abdomen

* nausea

* fever

* rapid pulse

Severe cases may cause dehydration and low blood pressure. The heart, lungs, or kidneys may fail. If bleeding occurs in the pancreas, shock and sometimes even death follow.

(Note: Pearl’s pain only had been present for eight hours before hospitalization – it didn’t occur when eating; she didn’t look or feel very sick until that evening, two hours after dinner. She had no fever, no bleeding in the pancreas.)

Besides asking about a person's medical history and doing a physical exam, a doctor will order a blood test to diagnose acute pancreatitis. During acute attacks, the blood contains at least three times more amylase and lipase than usual. Amylase and lipase are digestive enzymes formed in the pancreas. Changes may also occur in blood levels of glucose, calcium, magnesium, sodium, potassium, and bicarbonate. After the pancreas improves, these levels usually return to normal.

A doctor may also order an abdominal ultrasound to look for gallstones and a CAT (computerized axial tomography) scan to look for inflammation or destruction of the pancreas. CAT scans are also useful in locating pseudocysts.

(Note: CT scan showed nothing unusual. Lipase and amylase weren’t measured until 14 hours after admittance to the ER; amylase was 5 times normal while lipase was normal)

Acute pancreatitis can cause breathing problems. Many people develop hypoxia, which means that cells and tissues are not receiving enough oxygen. Doctors treat hypoxia by giving oxygen through a face mask. Despite receiving oxygen, some people still experience lung failure and require a ventilator.

Sometimes a person cannot stop vomiting and needs to have a tube placed in the stomach to remove fluid and air. In mild cases, a person may not eat for 3 or 4 days and instead may receive fluids and pain relievers through an intravenous line.

If an infection develops, the doctor may prescribe antibiotics. Surgery may be needed for extensive infections. Surgery may also be necessary to find the source of bleeding, to rule out problems that resemble pancreatitis, or to remove severely damaged pancreatic tissue.

Acute pancreatitis can sometimes cause kidney failure. If your kidneys fail, you will need dialysis to help your kidneys remove wastes from your blood.

If injury to the pancreas continues, chronic pancreatitis may develop. Chronic pancreatitis occurs when digestive enzymes attack and destroy the pancreas and nearby tissues, causing scarring and pain. The usual cause of chronic pancreatitis is many years of alcohol abuse, but the chronic form may also be triggered by only one acute attack, especially if the pancreatic ducts are damaged. The damaged ducts cause the pancreas to become inflamed, tissue to be destroyed, and scar tissue to develop.

While common, alcoholism is not the only cause of chronic pancreatitis. The main causes of chronic pancreatitis are

* alcoholism

* blocked or narrowed pancreatic duct because of trauma or pseudocysts have formed

* heredity unknown cause (idiopathic)

Other causes of chronic pancreatitis are

* congenital conditions such as pancreas divisum

* cystic fibrosis

* high levels of calcium in the blood (hypercalcemia)

* high levels of blood fats (hyperlipidemia or hypertriglyceridemia)

* some drugs

* certain autoimmune conditions

(Note: Pearl had gallbladder surgery 18 years earlier – perhaps duct was narrowed; also had recent history of high triglycerides possibly caused by the beta blocker high pressure med (Toprol-XL) she was taking. Pearl had a current immune system condition – Giant Cell Arteritis – active for the past nine years)

Most people with chronic pancreatitis have abdominal pain, although some people have no pain at all. The pain may get worse when eating or drinking, spread to the back, or become constant and disabling. In certain cases, abdominal pain goes away as the condition advances, probably because the pancreas is no longer making digestive enzymes. Other symptoms include nausea, vomiting, weight loss, and fatty stools.

People with chronic disease often lose weight, even when their appetite and eating habits are normal. The weight loss occurs because the body does not secrete enough pancreatic enzymes to break down food, so nutrients are not absorbed normally. Poor digestion leads to excretion of fat, protein, and sugar into the stool. If the insulin–producing cells of the pancreas (islet cells) have been damaged, diabetes may also develop at this stage.

(Note: Pearl did not have pain and wasn’t always nauseous, she didn’t have diabetes but did experience weight loss in the past several months. Stool tested normal in the ER.)

Lipase

Why get tested?

To diagnose and monitor pancreatitis or other pancreatic diseases

When to get tested?

When you have symptoms of a pancreatic disorder, such as severe abdominal pain, fever, loss of appetite, or nausea

What is being tested?

This test measures the amount of lipase in the blood. Lipase is one of several enzymes produced by the pancreas to help digest dietary fats, proteins, and carbohydrates. It is transported through the pancreatic duct and into the duodenum (beginning of the small intestine), where it helps break down dietary triglycerides (a form of fat) into fatty acids.

Lipase is usually present in the blood in small quantities. When cells in the pancreas are injured (as in pancreatitis) or the pancreatic duct is blocked (by a gallstone or rarely by a pancreatic tumor), increased amounts of lipase leak into the bloodstream, increasing blood concentrations.

How is it used?

The blood test for lipase is ordered, often along with an amylase test, to help diagnose and monitor acute pancreatitis (inflammation of the pancreas), chronic pancreatitis, and other disorders that involve the pancreas.

Lipase testing is also occasionally used in the diagnosis and follow-up of cystic fibrosis, celiac disease, and Crohn's disease.

When is it ordered?

A lipase test may be ordered when a patient has symptoms of a pancreatic disorder, such as severe abdominal pain, fever, loss of appetite, or nausea. It may also be ordered at intervals when a doctor wants to monitor a patient with a pancreas condition to evaluate the effectiveness of treatment and to determine whether the lipase levels are increasing or decreasing over time.

What does the test result mean?

In acute pancreatitis, lipase levels are frequently very high, often 5 to 10 times higher than the highest reference value (often called the upper limit of normal). In acute pancreatitis, lipase concentrations rise within 24 to 48 hours of an acute pancreatic attack and may remain elevated for about 5 to 7 days. Concentrations may also be increased with pancreatic duct obstruction, pancreatic cancer, and other pancreatic diseases.

Moderately increased lipase values may occur in other conditions such as kidney disease (due to decreased clearance from the blood), salivary gland inflammation, a bowel obstruction, or peptic ulcer disease, although the lipase test is not usually used to monitor these conditions. Decreased lipase levels may indicate permanent damage to the lipase-producing cells in the pancreas.

Since the reference values for lipase will vary from laboratory to laboratory, depending on the test method used, there is no universally accepted number that can be called normal or high.

Is there anything else I should know?

In acute pancreatitis, elevated lipase levels usually parallel blood amylase concentrations, although amylase levels tend to rise and fall a bit sooner than lipase levels. Drugs that may increase lipase levels include codeine, indomethacin, and morphine.

(Note: The narcotic methadone is a component of Darvocet N100 that Pearl had been taking for years)

Why get tested?

To diagnose and monitor pancreatitis or other pancreatic diseases

When to get tested?

When you have symptoms of a pancreatic disorder, such as severe abdominal pain, fever, loss of appetite, or nausea

What is being tested?

This test measures the amount of amylase in the blood or urine. Amylase is one of several enzymes produced by the pancreas to help digest fats, proteins, and carbohydrates It is secreted through the pancreatic duct into the duodenum (beginning of the small intestine), where it helps break down dietary carbohydrates. Amylase is also produced by other organs, particularly the salivary glands.

Amylase is usually present in the blood and urine in small quantities. When cells in the pancreas are injured (as in pancreatitis) or the pancreatic duct is blocked (by a gallstone or rarely by a pancreatic tumor), increased amounts of amylase find their way into the bloodstream, increasing concentrations in the blood and the urine, which is the excretion path for amylase from the blood.

How is it used?

The blood amylase test is ordered, often along with a lipase test, to help diagnose and monitor acute or chronic pancreatitis (inflammation of the pancreas) and other disorders that may involve the pancreas. A urine amylase test may also be ordered. Typically, its level will mirror blood amylase concentrations, but both the rise and fall occur later. Sometimes a urine creatinine clearance may be ordered along with the urine amylase to help evaluate kidney function since decreased kidney function can result in a slower rate of amylase clearance.

Amylase tests are sometimes used to monitor treatment of some cancers involving the pancreas and after removal of gallstones that have caused gallbladder attacks.

When is it ordered?

A blood amylase test may be ordered when a patient has symptoms of a pancreatic disorder, such as severe abdominal pain, fever, loss of appetite, or nausea. A urine amylase test may be ordered along with or following a blood amylase test. One or both may also be ordered when a doctor wants to monitor a patient to evaluate the effectiveness of treatment and to determine whether amylase levels are increasing or decreasing over time.

What does the test result mean?

In acute pancreatitis, amylase in the blood increases (often to 4-6 times higher than the highest reference value, sometimes called upper limit of normal). The increase occurs within 12 hours of injury to the pancreas and generally remains elevated until the cause is successfully treated. Then the amylase values will return to normal in a few days. In chronic pancreatitis, amylase levels initially will be moderately elevated but often decrease over time with progressive pancreas damage.

Amylase levels may also be significantly increased in patients with pancreatic duct obstruction, cancer of the pancreas, and gallbladder attacks. Urine and blood amylase levels may also be elevated with a variety of other conditions, such as ovarian cancer, lung cancer, tubal pregnancy, mumps, intestinal obstruction, or perforated ulcer, but amylase tests are not generally used to diagnose or monitor these disorders. Decreased blood and urine amylase levels may indicate permanent damage to the amylase-producing cells in the pancreas. Increased blood amylase levels with normal to low urine amylase levels may indicate decreased kidney function or the presence of a macroamylase, a benign complex of amylase and other proteins that accumulates in the blood.

Since reference values for amylase vary from laboratory to laboratory, depending on the test method used, there is no universally accepted number that can be called normal or high.

Is there anything else I should know?

In acute pancreatitis, elevated amylase levels usually parallel lipase concentrations, although lipase levels may take a bit longer to rise than blood amylase levels and will remain elevated longer.

Chronic pancreatitis is often associated with alcoholism. It may also be caused by trauma, pancreatic duct obstruction, and seen in association with genetic abnormalities such as cystic fibrosis. Amylase levels may be moderately elevated with chronic pancreatitis but often decrease over time with progressive pancreas damage.

Common Questions

1. Can medications that I am taking affect the amylase level? Yes. Some drugs that may cause amylase to rise include aspirin, diuretics, oral contraceptives, corticosteroids, indomethacin, ethyl alcohol, and opiates.

(Note: Pearl was taking a diuretic, corticosteroid and methadone – an opiate - on a regular basis for years)

Pearl had normal blood pressure and lung capacity before the paramedics arrived. The paramedics administered two intranasal bolus doses of Versed to Pearl at home. They should not have done that. They advised the ER staff of dosing with inhaled Versed upon admittance of Pearl to the ER. She arrived at the ER with two unusual symptoms reflecting hypersensitivity to Versed – respiratory depression and hypotension. In the ER Pearl was administered four additional sedatives in the ER despite the initial symptoms of hypersensitivity already present. Hydrocodone was given to Pearl by an ER nurse for pain control. Versed was administered to Pearl by the ER pulmonologist with two other sedatives. A half hour later arteries to arms and legs were no longer pulsatile – one indication of shock. The ER physician administered Versed again while Pearl was in shock – all sedatives given were contraindicated for Pearl.

Information is provided regarding the sedatives administered to Pearl in the ER: Versed, Dilaudid, hydrocodone, Levophed and Etomidate.

Class: Benzodiazepine tranquilizer.

Actions: Hypnotic, sedative.

Indications: Premedication prior to cardioversion/RSI, acute anxiety states.

Contraindications: Patients with known hypersensitivity to the drug, narrow-angle glaucoma, shock.

Side Effects: Drowsiness, hypotension, amnesia, respiratory depression, apnea.

Routes: IV, IM, intranasal.

The sedative effect of VERSED is accentuated by any concomitantly administered medication which depresses the central nervous system particularly narcotics (eg morphine meperidine and fentanyl) propofol ketamine nitrous oxide secobarbital and droperidol.

(Note: Pearl had been taking Darvocet N100 which has an opiate component. Versed was used in the ER for the intubation procedure. Despite the contraindication of Versed to a patient in shock, the ER physician administered Versed again while Pearl was in shock.)

VERSED®

Roche

Action And Clinical Pharmacology: General: Adult and Pediatric:

I.V. midazolam has been associated with respiratory depression and respiratory arrest, especially when used for sedation in noncritical care settings. In some cases, where this was not recognized promptly and treated effectively, death or hypoxic encephalopathy has resulted. I.V. midazolam should be used only in hospital or ambulatory care settings that provide for continuous monitoring of respiratory and cardiac function, i.e., pulse oximetry. Immediate availability of resuscitative drugs and age and size-appropriate equipment for bag/valve/mask ventilation and intubation, and personnel trained in their use and skilled in airway management should be assured (see Warnings). For deeply sedated patients, a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure.

Outside the ICU setting, marked i.v. sedation must be avoided in elderly or debilitated patients. All patients receiving midazolam for i.v. sedation should, of course, remain sufficiently alert to respond appropriately to verbal requests.

(Note: Pearl was not conscious when in shock yet the ER physician administered Versed to her.)

Manufacturers' Warnings In Clinical States:

Midazolam injection must never be used without individualization of dose. The immediate availability of oxygen and other appropriate medication, and the equipment necessary for resuscitation, the maintenance of a patent airway, support of ventilation and cardiac function should be ensured prior to the use of i.v. midazolam in any dose.

Because i.v. midazolam depresses respiration and because opioid agonists and other sedatives can add to this depression, midazolam should be administered as an induction agent only by a person trained in general anesthesia and should be used for sedation/anxiolysis/amnesia only in the presence of personnel skilled in early detection of hypoventilation, maintenance of a patent airway and support of ventilation.

Patients should be continuously monitored for early signs of hypoventilation or apnea which can lead to hypoxia/cardiac arrest unless effective countermeasures are taken. This should include pulse oximetry. Vital signs should continue to be monitored during the recovery period. Opioid agonists and other sedatives add to the respiratory depression produced by midazolam.

Midazolam should be used for i.v. sedation only with caution and must not be administered by single bolus or rapid i.v. administration.

(Note: Paramedics had Pearl inhale twice deeply from a nasal inhaler – this constitutes two bolus doses that should not have been administered).

Doses used for i.v. sedation should be always restricted to the special low levels recommended (see Dosage) and careful attention should be given in the selection and exclusion of patients that might be specially susceptible to adverse cardiac and respiratory reactions. Older chronically ill patients and those with concomitant use of other cardiorespiratory depressant agents are also especially susceptible to adverse reactions. It should be borne in mind that a fall in oxygen saturation will increase the probability of arrhythmias and other potentially fatal events in susceptible patients. Oxygen supplementation should be used in elderly patients with chronic respiratory or cardiac disease and patients who are seriously ill. Experience in the administration of drugs for i.v. sedation, continuous monitoring of patients to detect reversible adverse effects which may occur in individual patients and the means and setting required for immediate management of these patients are essential prior to the administration of midazolam for i.v. sedation.

Serious cardiorespiratory events have occurred. These have included respiratory depression, apnea, respiratory arrest and/or cardiac arrest, sometimes resulting in death. Strict adherence to the cautions and warnings recommended in the use of this drug is therefore required in order to minimize the incidence of these reactions.

Outside the ICU setting, midazolam should not be administered to patients in shock, coma, acute alcoholic intoxication, renal failure, or with severe depression of vital signs. Extreme care must be used in administering midazolam, particularly by the i.v. route to the elderly, to very ill patients and to those with limited pulmonary reserve due to the possible occurrence of excessive sedation and/or of apnea or respiratory depression. Patients with chronic obstructive pulmonary disease are unusually sensitive to the respiratory depressant effect of midazolam.

Myasthenic patients have the potential for respiratory decompensation if a substance with CNS-depressant and/or muscle-relaxant properties is administered. However, those myasthenic patients with established respiratory failure will need mechanical ventilation and for this sedation will be necessary. Careful monitoring of the patients is recommended should midazolam be used for sedation.

Concomitant use of barbiturates, alcohol, opiates or other CNS depressants increases the risk of apnea and may contribute, to excessive and/or prolonged drug effect.

Midazolam should not be given with a narcotic as an i.m. combination for premedication due to the risk of apnea. If a narcotic premedication is given, the subsequent i.v. dose of midazolam should be reduced.

Hypersensitivity: allergic reactions, including anaphylactic shock.

http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20V)/VERSED.html

DILAUDID is indicated for the management of pain in patients where an opioid analgesic is appropriate.

WARNING: ALCOHOL, OTHER OPIOIDS AND CENTRAL NERVOUS SYSTEM DEPRESSANTS (SEDATIVE-HYPNOTICS) POTENTIATE THE RESPIRATORY DEPRESSANT EFFECTS OF HYDROMORPHONE, INCREASING THE RISK OF RESPIRATORY DEPRESSION THAT MIGHT RESULT IN DEATH.

The major hazards of DILAUDID include respiratory depression and apnea. To a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest have occurred.

The concomitant use of other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers and alcohol may produce additive depressant effects. Respiratory depression, hypotension and profound sedation or coma may occur. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Opioid analgesics, including DILAUDID, may enhance the action of neuromuscular blocking agents and produce an excessive degree of respiratory depression.

Hypotensive Effect:

Opioid analgesics may cause severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume, or a concurrent administration of drugs such as phenothiazines or general anesthetics. Therefore, DILAUDID should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.

Sulfites:

Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Warnings & Precautions

Respiratory Depression: Respiratory depression is the chief hazard of DILAUDID. Respiratory depression is more likely to occur in the elderly, in the debilitated, and in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.

Special Risk Patients:

DILAUDID should be given with caution and the initial dose should be reduced in the elderly or debilitated and those with severe impairment of hepatic, pulmonary or renal functions; myxedema or hypothyroidism; adrenocortical insufficiency (e.g., Addison's Disease); CNS depression or coma; toxic psychoses; prostatic hypertrophy or urethral stricture; gall bladder disease; acute alcoholism; delirium tremens; kyphoscoliosis or following gastrointestinal surgery.

Geriatric Use:

Clinical studies of DILAUDID did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Serious overdosage with DILAUDID is characterized by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes bradycardia and hypotension. In serious overdosage, particularly following intravenous injection, apnea, circulatory collapse, cardiac arrest and death may occur.

Supportive measures (including oxygen, vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.

http://www.rxlist.com/cgi/generic/hydromorphone_wcp.htm

Note: Dilaudid was administered to Pearl by IV (0.5 mg) in the ER starting at 8:40 am on 10/18/07, a few hours after admittance. This should not have been administered for several reasons:

1. She was already being treated upon arrival for depressed respiration and hypotension caused by Versed administered at home by the paramedics. Dilaudid would intensify these symptoms.
2. She was elderly, debilitated and suspected of having renal and liver function degradation, and known to have adrenocortical insufficiency requiring prednisone supplementation.
3. She was known to be allergic to sulfites and sulfa compounds. She was asthmatic.

For the relief of moderate to moderately severe pain.

The most frequently observed adverse reactions include lightheadedness, dizziness, sedation, nausea, and vomiting.

Respiratory Depression: Hydrocodone bitartrate may produce dose-related respiratory depression by acting directly on the brain stem respiratory center. Hydrocodone also affects the center that controls respiratory rhythm and may produce irregular and periodic breathing.

The administration of narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

Special Risk Patients: As with any narcotic analgesic agent, hydrocodone bitartrate and acetaminophen tablets should be used with caution in elderly or debilitated patients, and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy or urethral stricture. The usual precautions should be observed and the possibility of respiratory depression should be kept in mind.

Note: This medication should not have been given to Pearl on 10/18/07 in the ER. She presented to the ER with vomiting. She had respiratory depression upon arrival at the ER. She had acute abdominal distress. She was elderly and debilitated and needed corticosteroid supplementation as would an Addison’s disease patient.

For blood pressure control in certain acute hypotensive states (e.g., pheochromocytomectomy, sympathectomy poliomyelitis, spinal anesthesia, myocardial infarction septicemia, blood transfusion, and drug reactions).

As an adjunct in the treatment of cardiac arrest and profound hypotension.

The following reactions can occur:

Ischemic injury due to potent vasoconstrictor action and tissue hypoxia. Respiratory difficulty.

Prolonged administration of any potent vasopressor may result in plasma volume depletion which should be continuously corrected by appropriate fluid and electrolyte replacement therapy. If plasma volumes are not corrected, hypotension may recur when Norepinephrine Bitartrate Injection, USP, is discontinued, or blood pressure may be maintained at the risk of severe peripheral and visceral vasoconstriction (e.g., decreased renal perfusion) with diminution in blood flow and tissue perfusion with subsequent tissue hypoxia and lactic acidosis and possible ischemic injury.

http://www.rxlist.com/cgi/generic/norepinephrine_ad.htm

Note: Levophed drip was started at 4:50 pm, 10/18/07, to facilitate intubation. It should not have been given to Pearl in her condition at that time. Within an hour her arm and leg arteries shut down. Kidneys degraded. Lactic acidosis became significantly elevated above normal.

Etomidate (Precedex) – ER medicine

Precedex is a variant of Etomidate (10 mg) that was administered in addition to Versed (4 mg) by the pulmonologist when performing the Endotracheal Intubation at 5:10 pm on 10/18/07.

PRECEDEX is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting.

The most frequently observed treatment-emergent adverse events included hypotension, hypertension, nausea, bradycardia, fever, vomiting hypoxia, tachycardia and anemia.

Co-administration of PRECEDEX with anesthetics, sedatives, hypnotics, and opioids is likely to lead to an enhancement of effects. Specific studies have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil, and midazolam.

Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of Precedex.

http://www.rxlist.com/cgi/generic/precedex_ad.htm

Note: After all the sedation Pearl appeared to be comatose. Her eyes were wide open but not responsive. The sedatives, Etomidate, Levophed and Versed administered by the pulmonologist were an added burden to sedatives administered earlier – Versed by the paramedics, Dilaudid by the ER physician and hydrocodone by the ER nurse. She was given Dilaudid though she was asthmatic and allergic to sulfites which can initiate anaphylactic shock. Her peripheral arteries were already restricted by Giant Cell Arteritis inflammation; Levophed and Etomidate were additional vasoconstrictors. These sedatives were contraindicated in Pearl’s treatment.