Sputum Examination

A sputum sample can be obtained by expectoration, tracheal suction, or bronchoscopy (discussed later). In addition to the analysis of the amount, quality, and color of the sputum (previously discussed in Chapter 2, page 44), the sputum sample may be examined for (1) culture and sensitivity, (2) Gram stain, (3) acid-fast smear and culture, and (4) cytology.

For a culture and sensitivity study, a single sputum sample is collected in a sterile container. This test is performed to diagnose bacterial infection, select an antibiotic, and evaluate the effectiveness of antibiotic therapy. The turnaround time for this test is 48 to 72 hours. The Gram staining of sputum is performed to classify bacteria into gram-negative organisms and gram-positive organisms. The results of the Gram stain tests guide therapy until the culture and sensitivity results are obtained. Box 8-1 presents common organisms associated with respiratory disorders. All but the viral organisms can be seen on a Gram stain.

The acid-fast smear and culture is performed to determine the presence of acid-fast bacilli (e.g., Mycobacterium tuberculosis). A series of three early morning sputum samples is tested. Cytology examination entails the collection of a single sputum sample in a special container with fixative solution. The sample is evaluated under a microscope for the presence of abnormal cells that may indicate a malignant condition.

The amount, color, and constituents of the sputum are often important in the assessment and diagnosis of many respiratory disorders, including tuberculosis, pneumonia, cancer of the lungs, and pneumoconiosis. For example, yellow sputum indicates an acute infection. Green sputum is associated with old, retained secretions. Green and foul-smelling secretions are frequently found in patients with anaerobic or Pseudomonas infection. Thick, stringy, and white or mucoid sputum suggests bronchial asthma. Brown sputum suggests the presence of old blood. Red sputum indicates fresh blood.

Skin Tests

Skin tests are commonly performed to evaluate allergic reactions or exposure to tuberculous bacilli or fungi. Skin tests entail the intradermal injection of an antigen. A positive test result indicates that the patient has been exposed to the antigen. However, it does not mean that the disease is actually present. A negative test result indicates that the patient has had no exposure to the antigen. A negative test result also may be seen in patients with a depression of cell-mediated immunity (anergy), such as that which develops in human immunodeficiency virus (HIV) infections.

Endoscopic Examinations

Bronchoscopy

A bronchoscopy is a well-established diagnostic and therapeutic tool used by a number of medical specialists, including those in intensive care units, special procedure rooms, and outpatient settings. With minimal risk to the patient—and without interrupting the patient’s ventilation—the flexible fiberoptic bronchoscope allows direct visualization of the upper airways (nose, oral cavity, and pharynx), larynx, vocal cords, subglottic area, trachea, bronchi, lobar bronchi, and segmental bronchi down to the third or fourth generation. Under fluoroscopic control, more peripheral areas can be examined or treated (Figure 8-1). Bronchoscopy may be diagnostic or therapeutic.

A diagnostic bronchoscopy is usually performed when an infectious disease is suspected and not otherwise diagnosed or to obtain a lung biopsy sample when the abnormal lung tissue is located on or near the bronchi. A diagnostic bronchoscopy is indicated for a number of clinical conditions, including further inspection and assessment of (1) abnormal radiographic findings (e.g., question of bronchogenic carcinoma or the extent of a bronchial tumor or mass lesion), (2) persistent atelectasis, (3) excessive bronchial secretions, (4) acute smoke inhalation injuries, (5) intubation damage, (6) bronchiectasis, (7) foreign bodies, (8) hemoptysis, (9) lung abscess, (10) major thoracic trauma, (11) stridor or localized wheezing, and (12) unexplained cough.

A videotape or colored picture of the procedure may also be obtained to record any abnormalities. When abnormalities are found, additional diagnostic procedures include brushings, biopsies, needle aspirations, and washings. For example, a common diagnostic bronchoscopic technique, termed bronchoalveolar lavage (BAL), involves injecting a small amount (30 mL) of sterile saline through the bronchoscope and then withdrawing the fluid for examination of cells. BAL is commonly used to diagnose Pneumocystis carinii pneumonia.

Therapeutic bronchoscopy includes (1) suctioning of excessive secretions or mucous plugs, especially when lung atelectasis is forming, (2) the removal of foreign bodies or cancer obstructing the airway, (3) selective lavage (with normal saline or mucolytic agents), and (4) management of life-threatening hemoptysis. Although the virtues of therapeutic bronchoscopy are well established, routine respiratory therapy modalities at the patient’s bedside (e.g., chest physical therapy, intermittent percussive ventilation [IPV], postural drainage, deep breathing and coughing techniques, and positive expiratory pressure [PEP] therapy) are considered the first line of defense in the treatment of atelectasis from pooled secretions. Clinically, therapeutic bronchoscopy is commonly used in the management of bronchiectasis, lung abscess, smoke inhalation and thermal injuries, and lung cancer (see Bronchopulmonary Hygiene Therapy Protocol 9-2, page 120).

Mediastinoscopy

Mediastinoscopy is the insertion of a scope through a small incision in the suprasternal notch; the scope is then advanced into the mediastinum. The test is used to inspect and biopsy lymph nodes in the mediastinal area. This procedure is performed to diagnose carcinoma, granulomatous infections, and sarcoidosis. Mediastinoscopy is done in the operating room while the patient is under general anesthesia.

Lung Biopsy

A lung biopsy sample can be obtained by means of a transbronchial needle biopsy or an open-lung biopsy. A transbronchial lung biopsy entails passing a forceps or needle through a bronchoscope to obtain a specimen (Figure 8-2). An open lung biopsy involves surgery to remove a sample of lung tissue. An incision is made over the area of the lung from which the tissue sample is to be collected. In some cases a large incision may be necessary to reach the suspected problem area. After the procedure a chest tube is inserted for drainage and suction for 7 to 14 days. An open-lung biopsy is usually performed when either a bronchoscopic biopsy or a needle biopsy has been unsuccessful or cannot be performed or when a larger piece of tissue is necessary to establish a diagnosis.

An open biopsy requires general anesthesia and is more invasive and thus more likely to cause complications. Overall, the risks include pneumothorax, bleeding, bronchospasm, heart arrhythmias, and infection. A needle lung biopsy is contraindicated in patients with lung bullae, cysts, blood coagulation disorders of any type, severe hypoxia, pulmonary hypertension, or cor pulmonale.

A lung biopsy is usually performed to diagnose abnormalities identified on a chest radiograph or computed tomography (CT) scan that are not readily accessible by other diagnostic procedures, such as bronchoscopy. A lung biopsy is especially useful in investigating peripheral lung abnormalities, such as recurrent infiltrates and pleural or subpleural lesions. Additional conditions under which a lung biopsy may be performed include metastatic cancer to the lung and pneumonia with lung abscess.

The tissues from a lung biopsy are sent to a pathology laboratory for examination of malignant cells. Other samples may be sent to a microbiology laboratory to determine the presence of infection. Lung biopsy results are usually available in 2 to 4 days. In some cases, however, it may take several weeks to confirm (by culture) certain infections, such as tuberculosis.

Video-Assisted Thoracoscopy

In video-assisted thoracoscopy (VATS), a newly developed technique, a small incision is made in the chest wall, and a device called a thoracoscope is inserted. This device is equipped with a fiberscope that can examine the pleural cavity. The results are displayed on a video monitor (as in bronchoscopy). When pleural lesions are identified, they can be biopsied under video guidance. This procedure is helpful in the diagnosis of tuberculosis, mesothelioma, and metastatic cancer.

Thoracentesis

Thoracentesis (also called thoracocentesis) is a procedure in which excess fluid accumulation (pleural effusion) between the chest cavity and lungs (pleural space) is aspirated through a needle inserted through the chest wall (Figure 8-3). A chest radiograph, CT scan, or ultrasound scan may be used to confirm the precise location of the fluid. Once the fluid has been located, thoracentesis may be performed for diagnostic or therapeutic purposes.

Diagnostic thoracentesis may be performed to identify the cause of a pleural effusion. The analysis of the pleural fluid may be useful in the diagnosis and staging of a suspected or known malignancy. A pleural biopsy may also be performed during a thoracentesis to collect a tissue sample from the inner lining of the chest wall. Therapeutic thoracentesis may be performed to relieve shortness of breath or pain caused by a large pleural effusion, to remove air trapped between the lung and chest wall, or to administer medication directly into the lung cavity to treat the cause of the fluid accumulation or to treat cancer. The fluid in the lung cavity is classified as either a transudate or an exudate.

Transudates develop when fluid from the pulmonary capillaries moves into the pleural space. The fluid produced is thin and watery and usually has a low white blood cell (WBC) count, a low lactate dehydrogenase (LDH) enzyme level, and a low protein level. The pleural surfaces are not involved in producing the transudate. A transudate may be caused by left ventricular heart failure, cirrhosis, nephrotic syndrome, and peritoneal dialysis.

Exudates may be caused by a variety of conditions, including pulmonary infections (e.g., pneumonia, tuberculosis, and fungal diseases), cancer, chest trauma, pancreatitis, autoimmune disease, or a pulmonary embolism. When an infection is present, the fluid usually has a high WBC count, a high LDH enzyme level, a high protein level, a large amount of cellular debris, and the presence of bacteria or other infectious organisms. When cancer is present, the fluid usually has a high WBC count (often lymphocytes), a high LDH enzyme level, and a high protein level. Abnormal cells also may be found. When a pulmonary embolism is present, a large number of red blood cells (RBCs) are usually present and the WBC and protein levels are both low.

The thoracentesis procedure is generally performed while the patient is in an upright position, leaning forward slightly, typically over a bedside table. Using a local anesthetic, the physician inserts a large-bore thoracentesis needle (16 to 19 gauge), or needle-catheter, between the ribs over the fluid accumulation. The needle or catheter is connected to a small tube with a three-way stopcock, which in turn is attached to either a large syringe or a vacuum and collection bottle. Depending on the purpose of the thoracentesis, up to 1500 mL may be withdrawn. Once the fluid has been collected, the needle or catheter is removed and a bandage is placed over the puncture site. The patient is usually instructed to lie on the puncture site side for about an hour to allow the puncture site to seal.

A thoracentesis is usually a safe procedure. However, a chest radiograph is generally obtained shortly after the procedure to ensure that no complications have developed. Complications may include pneumothorax, pulmonary edema (which sometimes occurs when large amounts of fluid are aspirated), infection, bleeding, and organ damage.

Pleurodesis

Pleurodesis is performed to prevent the recurrence of a pneumothorax or pleural effusion. Pleurodesis is achieved by injecting any number of agents (called sclerosing agents or sclerosants) into the pleural space through a chest tube. There is no one sclerosant that is more effective or safer than the others. Common sclerosant chemicals include a slurry of talc, bleomycin, nitrogen mustard, doxycycline, povidone iodine, or quinacrine. The instilled sclerosing agents cause irritation and inflammation (pleuritis) between the parietal and the visceral layers of the pleura. This action causes the pleurae to stick together and thereby prevents subsequent gas or fluid accumulation.

A chemical pleurodesis is considered to be the standard of care for patients with malignant pleural effusion. Because chemical pleurodesis is a painful procedure, the patient is premedicated with a sedative and analgesics. A local anesthetic may also be instilled into the pleural space or added to the sclerosant. Although complications of pleurodesis are uncommon, risks include the following:

Complications may be specific for each sclerosant.

Pleurodesis may fail because of the following complications:

Hematology, Blood Chemistry, and Electrolyte Findings

Abnormal hematology, blood chemistry, or electrolyte values assist the respiratory care practitioner and physician in the assessment of cardiopulmonary disorders. Knowledge of these laboratory tests provides a greater understanding of the clinical manifestations of a particular cardiopulmonary disorder.

Hematology

The most frequent laboratory hematology test is the complete blood count (CBC). The CBC provides important information about the patient’s diagnosis, prognosis, response to treatment, and recovery. The CBC includes the red blood cell (RBC) count, hemoglobin (Hb), hematocrit (Hct), the total WBC count, and at least an estimate of the platelet count.

Red Blood Cell Count

The RBCs (erythrocytes) constitute the major portion of the blood cells. The healthy man has about 5 million RBCs in each cubic millimeter (mm³) of blood. The healthy woman has about 4 million RBCs in each cubic millimeter of blood. Clinically, the total number of RBCs and the RBC indices are useful in assessing the patient’s overall oxygen-carrying capacity. The RBC indices are helpful in the identification of specific RBC deficiencies. Table 8-1 provides an overview of the red blood cell indices and types of anemias.

Table 8-1

Red Blood Cell Indices

Index	Description
Hematocrit (Hct)	The Hct is the volume of red blood cells (RBCs) in 100 mL of blood and is expressed as a percentage of the total volume. In the healthy man the Hct is about 45%; in the healthy woman the Hct is about 42%. In the healthy newborn the Hct ranges from 45% to 60%. The Hct also is called the packed cell volume (PCV).
Hemoglobin (Hb)	Most of the oxygen that diffuses into the pulmonary capillary blood rapidly moves into the RBCs and chemically attaches to the Hb. Each RBC contains approximately 280 million Hb molecules. The Hb value is reported in grams per 100 mL of blood (also referred to as grams percent of hemoglobin [g% Hb]). The normal Hb value for men is 14 to 16 g%. The normal Hb value for women is 12 to 15 g%. Hb constitutes about 33% of the RBC weight.
Mean cell volume (MCV)	The MCV is the actual size of the RBCs and is used to classify anemias. It is an index that expresses the volume of a single red cell and is measured in cubic microns. The normal MCV is 87 to 103 cubic microns for both men and women.
Mean corpuscular hemoglobin concentration (MCHC)	The MCHC is a measure of the concentration or proportion of Hb in an average (mean) RBC. The MCHC is derived by dividing the g% Hb by the Hct. For example, if a patient has 15 g% Hb and an Hct of 45%, the MCHC is 33%. The normal MCHC for men and women ranges from 32% to 36%. The MCHC is most useful in assessing the degree of anemia because the two most accurate hematologic measurements (Hb and Hct—not RBC) are used for the test.
Mean cell hemoglobin (MCH)	The MCH is a measure of weight of Hb in a single RBC. This value is derived by dividing the total Hb (g% Hb) by the RBC count. The MCH is useful in diagnosing severely anemic patients but not as good as the MCHC because the RBC is not always accurate. The normal range for the MCH is 27 to 32 picograms per RBC.
Types of Anemias
Normochromic (normal Hb) and normocytic (normal cell size) anemia	Normochromic anemia is most commonly caused by excessive blood loss. The amount of Hb and the number of RBCs are decreased, but the individual size and content remain normal. Clinically, the laboratory report reveals the following: Hct: below normal Hb: below normal MCV: normal MCHC: normal MCH: normal

Hypochromic (decreased Hb) microcytic (small cell size) anemia In hypochromic anemia the size of the RBCs and the Hb content are decreased. This form of anemia is commonly seen in patients with chronic blood loss, iron deficiency, chronic infections, and malignancies. Clinically, the laboratory report reveals the following:

Hct: below normal

Hb: below normal

MCV: below normal

MCHC: below normal

MCH: below normal

Macrocytic (large cell size) anemia Macrocytic anemia is commonly caused by folic acid and vitamin B₁₂ deficiencies. Patients with macrocytic anemia produce fewer RBCs, but the RBCs that are present are larger than normal. Clinically, the laboratory report reveals the following:

Hct: below normal

Hb: below normal

MCV: above normal (because of the larger RBC size)

MCHC: above normal (because of the larger RBC size)

White Blood Cell Count

The major functions of the white blood cell count (WBCs) (leukocytes) are to (1) fight against infection, (2) defend the body by phagocytosis against foreign substances, and (3) produce (or at least transport and distribute) antibodies in the immune response. The WBCs are far less numerous than the RBCs, averaging 5000 to 10,000 cells per cubic millimeter of blood. There are two types of WBCs: granular leukocytes and nongranular leukocytes. Because the general function of the leukocytes is to combat inflammation and infection, the clinical diagnosis of an injury or infection often entails a differential count, which is the determination of the number of each type of cell in 100 WBCs. Box 8-2 shows a normal differential count. Table 8-2 provides an overview of cell types and common causes for their increase (leukocytosis).

Granular Leukocytes

The granular leukocytes (also called granulocytes) are so classified because of the granules present in their cytoplasm. The granulocytes are further divided into the following three types according to the staining properties of the granules: neutrophils, eosinophils, and basophils. Because these cells have distinctive multilobar nuclei, they are often referred to as polymorphonuclear leukocytes.

Neutrophils

The neutrophils comprise about 60% to 70% of the total number of WBCs. They have granules that are neutral and therefore do not stain with an acid or a basic dye. The neutrophils are the first WBCs to arrive at the site of inflammation, usually appearing within 90 minutes of the injury. They represent the primary defense against bacterial organisms through the process of phagocytosis. The neutrophils are one of several types of cells called phagocytes that ingest and destroy bacterial organisms and particulate matter. The neutrophils also release an enzyme called lysozyme, which destroys certain bacteria. An increased neutrophil count is associated with (1) bacterial infection, (2) physical and emotional stress, (3) tumors, (4) inflammatory or traumatic disorders, (5) some leukemias, (6) myocardial infarction, and (7) burns.

Early forms of neutrophils are nonsegmented and are called “band” forms. They almost always signify infection if elevated above 10% of the differential. More mature forms of neutrophils have segmented nuclei. They may increase even in the absence of infection (e.g., with stress [exercise] or the use of corticosteroid medication).

Eosinophils

The cytoplasmic granules of the eosinophils stain red with the acid dye eosin. These leukocytes comprise 2% to 4% of the total number of WBCs. Although the precise function of the eosinophils is unknown, they are thought to play a role in the breakdown of protein material. It is known, however, that the eosinophils are activated by allergies (such as an allergic asthmatic episode) and parasitic infections. Eosinophils are thought to detoxify the agents or chemical mediators associated with allergic reactions. An increased eosinophil count also may be associated with lung cancer, chronic skin infections (e.g., psoriasis, scabies), polycythemia, and tumors.

Basophils

The basophils comprise only about 0.5% to 1% of the total white blood count. The granules of the basophils stain blue with a basic dye. The precise function of the basophils is not clearly understood. Increased basophils are primarily associated with certain myeloproliferative disorders. It is thought that the basophils are involved in allergic and stress responses. They also are considered to be phagocytic and to contain heparin, histamines, and serotonin.

Nongranular Leukocytes

There are two groups of nongranular leukocytes, the monocytes and lymphocytes. The term mononuclear leukocytes also is used to describe these cells because they do not contain granules but have spheric nuclei.

Monocytes

The monocytes are the second order of cells to arrive at the inflammation site, usually appearing approximately 5 hours or more after the injury. After 48 hours, however, the monocytes are usually the predominant cell type in the inflamed area. The monocytes are the largest of the WBCs and comprise about 3% to 8% of the total leukocyte count. The monocytes are short-lived, phagocytic WBCs, with a half-life of approximately 1 day. They circulate in the bloodstream, from which they move into tissues—at which point they may mature into long-living macrophages (also called histiocytes). The macrophages are large wandering cells that engulf larger and greater quantities of foreign material than the neutrophils. When the foreign material cannot be digested by the macrophages, the macrophages may proliferate to form a capsule that surrounds and encloses the foreign material (e.g., fungal spores). Although the monocytes and macrophages do not respond as quickly to an inflammatory process as the neutrophils, they are considered one of the first lines of inflammatory defense. Therefore an elevated number of monocytes suggests infection and inflammation. The monocytes play an important role in chronic inflammation and also are involved in the immune response and malignancies.

Lymphocytes

Increased lymphocytes are typically seen in viral infections (e.g., infectious mononucleosis). The lymphocytes also are involved in the production of antibodies, which are special proteins that inactivate antigens. For a better understanding of the importance of the lymphocytes and the clinical significance of their destruction or depletion (e.g., in acquired immunodeficiency syndrome [AIDS]), a brief review of the role and function of the lymphocytes in the immune system is in order.

The lymphocytes can be divided into two categories: B cells and T cells. These cells can be identified with an electron microscope according to certain distinguishing surface marks, called rosettes: T cells have a smooth surface; B cells have projections. B cells comprise 10% to 30% of the total lymphocytes; T cells comprise 70% to 90% of the total lymphocytes.

The B cells, which are formed in the bone marrow, further divide into either plasma cells or memory cells. The plasma cells secrete antibodies in response to foreign antigens. The memory cells retain the ability to recognize specific antigens long after the initial exposure and therefore contribute to long-term immunity against future exposures to invading pathogens.

The T cells, which are formed in the thymus, are further divided into four functional categories: (1) cytotoxic T cells (also called killer lymphocytes or natural killer cells), which attack and kill foreign or infected cells; (2) helper T cells, which recognize foreign antigens and help activate cytotoxic T cells and plasma cells (B cells); (3) inducer T cells, which stimulate the production of the different T-cell subsets; and (4) suppressor T cells, which work to suppress the responses of the other cells and help provide feedback information to the system.

The T cells also may be classified according to their surface antigens (i.e., the T cells may display either T4 antigen or T8 antigen). The T4 surface antigen subset, which comprises 60% to 70% of the circulating T cells, consists mainly of the helper and inducer cells. The T8 surface antigen subset consists mainly of the cytotoxic and suppressor cells.

Sequence of Lymphocyte Responses to Infection

Initially, the macrophages attack and engulf the foreign antigens. This activity in turn stimulates the production of T cells and, ultimately, the antibody-producing B cells (plasma cells). The T4 cells play a pivotal role in the overall modulation of this immune response by (1) secreting a substance called lymphokine, which is a potent stimulus to T-cell growth and differentiation; (2) recognizing foreign antigens; (3) causing clonal proliferation of T cells; (4) mediating cytotoxic and suppressor functions; and (5) enabling B cells to secrete specific antibodies.

Because T cells (especially the T4 lymphocytes) have such a central role in this complex immune response, it should not be difficult to imagine the devastating effect that would ultimately follow from the systematic depletion of T lymphocytes. For example, virtually all the infectious complications of AIDS may be explained with reference to the effect that HIV has on the T cells. A decreased number of T cells increases the patient’s susceptibility to a wide range of opportunistic infections and neoplasms. In the healthy subject, the T4/T8 ratio is about 2.0. In the HIV-infected patient with AIDS, the T4/T8 ratio is usually 0.5 or less.

Platelet Count

Platelets (also called thrombocytes) are the smallest of the formed elements in the blood. They are round or oval, flattened, and disk-shaped in appearance. Platelets are produced in the bone marrow and possibly in the lungs. Platelet activity is essential for blood clotting. The normal platelet count is 150,000 to 350,000/mm³.

A deficiency of platelets leads to prolonged bleeding time and impaired clot retention. A low platelet count (thrombocytopenia) is associated with (1) massive blood transfusion, (2) pneumonia, (3) cancer chemotherapy, (4) infection, (5) allergic conditions, and (6) toxic effects of certain drugs (e.g., heparin, isoniazid, penicillins, prednisone, streptomycin). A high platelet count (thrombocythemia) is associated with (1) cancer, (2) trauma, (3) asphyxiation, (4) rheumatoid arthritis, (5) iron deficiency, (6) acute infections, (7) heart disease, and (8) tuberculosis.

A platelet count of less than 20,000/mm³ is associated with spontaneous bleeding, prolonged bleeding time, and poor clot retraction. The precise platelet count necessary for hemostasis is not firmly established. Generally, platelet counts greater than 50,000/mm³ are not associated with spontaneous bleeding. Therefore various diagnostic or therapeutic procedures, such as bronchoscopy or the insertion of an arterial catheter, are usually safe when the platelet count is greater than 50,000/mm³.

Blood Chemistry

A basic knowledge of blood chemistry, normal values, and common health problems that alter these values is an important cornerstone of patient assessment. Table 8-3 lists the blood chemistry tests usually monitored in respiratory care.

Lactic dehydrogenase (LDH) 80 to 120 Wacker units Serum glutamic oxaloacetic transaminase (SGOT) 8 to 33 U/ml Aspartate aminotransferase (AST) 7 to 40 U/L (0.12-067 µKat/L) Increases are associated with the following:

Alanine aminotransferase (ALT) (previously called serum glutamic pyruvic transaminase [SGPT]) 5 to 36 U/L (0.08-0.6 µKat/L) Increases are associated with the following:

Bilirubin Blood urea nitrogen (BUN) 8 to 18 mg/dl Increases are associated with acute or chronic renal failure Serum creatinine 0.6 to 1.2 mg/dl Increases are associated with renal failure

Electrolytes

For the cells of the body to function properly, a normal concentration of electrolytes must be maintained. Therefore the monitoring of the electrolytes is extremely important in the patient whose body fluids are being endogenously or exogenously manipulated (e.g., intravenous therapy, renal disease, diarrhea). Table 8-4 lists electrolytes monitored in respiratory care.

Potassium (K⁺) 3.8 to 5.0 mEq/L     Chloride (Cl⁻) 95 to 103 mEq/L Calcium (Ca⁺⁺) 4.5 to 5.4 mEq/L Paresthesia, cramping of muscles, stridor, convulsions, mental disturbance, Chvostek’s sign, Trousseau’s sign