Lab Work: What, When, and How Often?

Jon Taveau

The probability of a normal person having normal laboratory results when multiple tests are performed is relatively low. For example, one abnormal test result is expected in almost 50% of patients having a Chem-12 and 60% having a Chem-20. Chem-12 is a routine laboratory panel on serum that includes: sodium, potassium, chloride, CO₂, creatinine, blood urea nitrogen [BUN], glucose, calcium, magnesium, phosphorus, albumin, total protein—also known as serum multiple analysis [SMA] 12. Chem-20 is also known as SMA 20. It is a routine panel of serum studies. Each lab determines the studies but typically it includes: albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, BUN, calcium chloride, CO₂, creatinine, total and direct bilirubin, γ-glutamyl transterase, glucose, lactate dehydrogenase (LDH), phosphorus, potassium, sodium, protein, magnesium, and uric acid.)

ACTH, adrenocorticotropic hormone; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogren; CBC, complete blood count; CK, creatine kinase; CK–MB, creatine kinase-MB mass; CMP, cytidine monophosphate; CSF, cerebrospinal fluid; DNA, deoxyribonucleic acid; ESR, erythrocyte sedimentation rate; FTA, fluorescent treponema absorption; HLA, human leukocyte antigen; Ig, immunoglobulin; INR, International Normalized Ratio; LDH, lactate dehydrogenase; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; PCR, polymerase chain reaction; RBC, red blood cell; TSH, thyroid-stimulating hormone; VDRL, venereal disease research laboratory; WBC, white blood cell.

Accuracy of laboratory values is also complicated by sex, age, diet, malnutrition, medications, time of day, and patient position. For example, plasma volume increases when the patient changes from upright to supine; age results in declining cardiac, pulmonary, renal, and metabolic functions; high serum potassium may be simply due to cellular release after prolonged tourniquet constriction or may be the result of hemolysis; low serum glucose may result in patients with high white blood cell (WBC) counts; or low serum sodium and high plasma hemoglobin may result in patients with hyperlipidemia.

Routine preoperative laboratory tests should include a hemogram with differential (WBC, hemoglobin, hematocrit, and platelets), an electrolyte panel (sodium, potassium, chloride, carbon dioxide, BUN, creatinine, and serum glucose), and coagulation studies (prothrombin time [PT], International Normalized Ratio [INR], and partial thromboplastin time [PTT]). Depending on age and clinical suspicion, electrocardiogram (EKG) and chest x-ray may be appropriate. For all intracranial procedures and extensive spine procedures, blood should be typed and crossed for possible transfusion. For other neurosurgical procedures, blood should at least be typed and screened. Ancillary laboratory tests should be ordered based on the preoperative assessment and according to American Society of Anesthesiologists (ASA) guidelines.

Radiologic studies and surgical biopsy are the primary methods used to diagnose central nervous system (CNS) tumors; however, diagnostic laboratory studies may assist with diagnosis and therapeutic monitoring. Pituitary tumors may produce endocrine abnormalities that may be measured in serum. Polycythemia is associated with hemangioblastoma, a posterior fossa tumor. Some parasellar and pineal region embryonal tumors secrete hormones and proteins: α-fetoprotein (AFP), β subunit of human chorionic gonadotropin (β-hCG), and placental alkaline phosphatase (PLAP). Cerebrospinal fluid (CSF) cytology may be used to diagnose tumor type. CSF analysis may reveal polyamines (putrecine) that localize tumors to ventricles or subarachnoid space, or a pleocytosis that may increase suspicion for lymphoma.

Astrocytomas, oligodendrogliomas, ependymomas, mixed gliomas, neuronal tumors, and other neoplastic processes of the CNS may be identified in CSF by cytology.

Pineal parenchymal tumors produce a characteristic clinical picture due to their proximity to the ventricular system. Opening pressure during lumbar puncture may be high due to obstructive hydrocephalus. Laboratory values reflecting endocrine dysfunction may be present in tumors invading the hypothalamus: diabetes insipidus, hypopituitarism, and precocious puberty. Biochemical tumor markers may suggest tumor type. Serum and CSF AFP, β-hCG, and PLAP levels are most commonly ordered to discriminate between choriocarcinoma or mixed germ cell tumors containing choriocarcinomatous elements (high β-hCG levels); germinomas, pineal parenchymal tumors, and teratomas (neither AFP nor β-hCG elevations); and germinomas (very high elevations of PLAP). However, tumor markers lack sufficient specificity and sensitivity to accurately predict tumor histology.

Pituitary tumors present clinically by symptoms of pituitary hypersecretion (70% of cases), symptoms of pituitary hyposecretion, or neurologic symptoms of compression of the pituitary or other adjacent sellar structures.

Hypersecretory syndromes include acromegaly, Cushing’s disease, amenorrhea-galactorrhea syndrome, and secondary hyperthyroidism from hypersecretion of growth hormone (GH), adrenocorticotropic hormone (ACTH), prolactin (PRL), and thyroid-stimulating hormone (TSH).

Hypopituitarism results in fatigue, weakness, hypogonadism, regression of secondary sexual characteristics, and hypothyroidism. Pituitary insufficiency also occurs acutely in pituitary apoplexy.

Diagnostic laboratory studies are very sensitive indicators of endocrine dysfunction and are focused on measuring pituitary and/or target-organ hormones in basal and provoked states to discriminate between various pituitary adenoma subtypes. Screening tests include (1) adrenal axis: morning serum cortisol, 24-hour urine free cortisol, dexamethasone suppression test, cosyntropin stimulation test, and insulin tolerance test; (2) thyroid axis: TSH, T4, and thyrotropin-releasing hormone (TRH) stimulation test; (3) gonadal axis: serum luteinizing hormone/follicle-stimulating hormone (LH/FSH); (4) prolactin levels: PRL; (5) growth hormone: somatomedin-C (insulin-like growth factor I [IGF-I]), growth hormone releasing hormone (GH-RH) stimulation test, and glucose suppression test; and (6) neurohypophysis: water deprivation test and serum antidiuretic hormone (ADH).

Primary CNS lymphoma (PCNSL) is lymphoma of the CNS in the absence of systemic lymphoma. Systemic lymphoma disseminates to the meninges and rarely to the brain parenchyma, whereas primary CNS lymphoma frequently start as periventricular lesions.

PCNSL is rare and accounts for only 1 to 2% of intracranial tumors. It occurs primarily in the elderly; however, patients having human immunodeficiency virus (HIV) and congenital immunodeficiencies, collagen vascular disease, and organ transplants are particularly at risk for primary CNS lymphoma.

CSF cytology may detect high-grade disease and involvement of lep-tomeninges. The CSF analysis may reveal elevations in protein and pleocyto-sis (immunohistochemical stains reveal monoclonal populations of cells); β₂-microglobulin, lactic acid dehydrogenase isoenzymes, and β-glucuronidase are elevated as well. Tissue biopsy is the preferred method of diagnosis of PCNSL. However, an unequivocally positive CSF cytology eliminates the need for brain biopsy.

Metastasis to the brain and spinal cord is common among cancer patients. Brain metastasis occurs in 20% and spinal cord metastasis in 10% of patients having primary malignancies of the lung (bronchogenic carcinoma, especially small-cell carcinomas), breast cancer, renal cell carcinoma, melanoma, and gastrointestinal malignancies.

Renal cell carcinoma is usually silent; symptoms of hematuria, palpable flank mass, and flank pain denote advanced disease. Renal cell carcinomas secrete hormones (parathyroid hormone and erythropoietin) that cause hypercalcemia and erythrocytosis. Stauffer’s syndrome is a reversible hepatorenal condition with abnormal results on liver function studies.

Following trauma, several delayed conditions may present. Diagnostic laboratory studies may be implemented to diagnose and/or prevent delayed hemorrhage, post-traumatic diffuse cerebral edema, seizures, metabolic abnormalities, and meningitis.

Initial or delayed hemorrhage may be anticipated in 75% of patients with traumatic brain injury. Epidural hematoma (EDH), subdural hematoma (SDH), or traumatic intracerebral hemorrhage (TICH) may be present in either initial or delayed fashions.

Coagulopathy is identified using PT, INR, PTT, bleeding time, and platelet count. Coagulopathy is treated with fresh frozen plasma (FFP) and vitamin K (phytonadione) and is carefully monitored using coagulation studies every 4 hours until it is corrected.

Phenytoin is the first-line antiseizure medication, and levels are observed as per the above protocol.

Increased cerebral blood volume may result from loss of cerebral vascular autoregulation. It occurs in children more frequently than in adults and when associated with severe head injury carries close to 100% rate of mortality.

Aggressive management of intracerebral pressure (ICP) is required. Along with general measures to lower ICP (elevation of HOB, sedation, normotension, and euvolemia), patients may be considered for hypertonic therapy with hypertonic saline or osmotic therapy using mannitol and Lasix. High tonicity (>320 mOsm/L) and hypovolemia (“running dry”) have little advantage to prevent cerebral edema and may result in renal dysfunction. Prevention of hypoglycemia is also important, as it aggravates cerebral edema.

Post-traumatic seizures may occur early (<7 days) or late (>7 days) following head trauma and may precipitate adverse events as the result of elevation of ICP, alterations in systolic blood pressure (SBP), changes in oxygenation, and excessive neurotransmitter release. Anticonvulsants may be used to prevent early post-traumatic seizures in patients that meet high-risk criteria: (1) presence of SDH, EDH, ICH, TICH, or delayed traumatic intracerebral hemorrhage (DTICH); (2) open-depressed skull fracture with parenchymal injury; (3) penetrating brain injury; or (4) seizure within the first 24 hours following trauma.

Patients meeting criteria should be started on phenytoin, carbamazepine, valproic acid, or phenobarbital for 1 week. Diagnostic laboratory studies to monitor AED levels are per specific agent:

Several metabolic disorders may result from trauma (directly or indirectly) that affect the CNS: hypoxia, hyponatremia, hypoglycemia, renal failure, and adrenal insufficiency, as well as hepatic encephalopathy.

Acute renal failure (ARF) is categorized as prerenal, postrenal, and intrinsic renal. Prerenal and postrenal causes are potentially reversible if diagnosed and treated early; some intrinsic renal causes that result in acute glomerular vascular and tubulointerstitial nephropathy are also treatable (malignant hypertension, glomerulonephritis, vasculitis, bacterial infections, electrolyte disorders [hypercalcemia], and drug reactions).

Prerenal azotemia (50–80% of ARF cases) results from inadequate renal perfusion caused by extracellular fluid volume depletion or cardiovascular disease. Postrenal azotemia (5–10% of ARF cases) results from various types of obstruction in the voiding and collecting systems. Intrinsic renal causes of ARF are the result of prolonged renal ischemia (hemorrhage, surgery) or a nephrotoxin.

Symptoms and signs relate to the loss of excretory function and depend on the degree of renal dysfunction, the rate of renal failure, and the cause (trauma, surgery). Preserved urine output of 1 to 2.4 L/day is common. Oliguria may occur; anuria suggests bilateral renal artery occlusion, obstructive uropathy, acute cortical necrosis, or rapidly progressive glomerulonephritis.

Secondary adrenal insufficiency may occur in panhypopituitarism, in isolated failure of ACTH production, in patients receiving corticosteroids, or after acute discontinuance of longer use of corticosteroid therapy without appropriate tapering.

Patients with secondary adrenal insufficiency are not hyperpigmented, as are those with Addison’s disease. They have relatively normal electrolyte levels. Hyperkalemia and elevated BUN are not present because of the near-normal secretion of aldosterone. Hyponatremia may occur on a dilutional basis. Patients with panhypopituitarism have depressed thyroid and gonadal function and hypoglycemia; coma may result when symptomatic secondary adrenal insufficiency occurs.

Hepatic encephalopathy may result from hepatic failure resulting from trauma. The liver metabolizes and detoxifies digestive products brought from the intestine by the portal vein. In hepatic failure, these products escape into the systemic circulation if portal blood bypasses parenchymal cells or if the function of these cells is severely impaired. The resulting toxic effect on the brain produces the clinical syndrome.

Personality changes (inappropriate behavior, altered mood, impaired judgment) are common early manifestations. Psychomotor testing can detect such abnormalities not suspected clinically. Usually, impaired consciousness occurs. Initially, subtle sleep pattern changes or sluggish movement and speech may be present. Drowsiness, confusion, stupor, and frank coma indicate increasingly advanced encephalopathy. Constructional apraxia, in which the patient cannot reproduce simple designs (a star), is a characteristic early sign. A musty sweet odor of the breath, fetor hepaticus, occurs. A peculiar, characteristic flapping tremor due to lack of attention, called asterixis, is elicited when the patient holds his or her arms outstretched with wrists dorsiflexed; as coma progresses, this sign disappears, and hyperreflexia and the Babinski response may occur. Agitation or mania may occur. Seizures and localizing neurologic signs may also occur.

Diagnostic laboratory studies for hepatic function include serum total protein, albumin, alkaline phosphatase, ALT, AST, total bilirubin, ammonia (NH₃), (GGT), prothrombin time, platelet count, and serum protein electrophoresis.

The diagnosis of hepatic encephalopathy is clinical. There is no correlation with liver function tests. Blood ammonia levels are elevated, but values correlate poorly with clinical status. The CSF is unremarkable except for mild protein elevation.

Post-traumatic meningitis occurs in up to 20% of patients with moderate to severe head injuries. Most cases occur within 2 weeks of trauma; 75% of cases have demonstrable basal skull fracture, and 50% have obvious CSF rhinorrhea.

Antibiotic coverage for active infection should empirically be broad-spectrum, targeting gram-positive, gram-negative, and anaerobic organisms until culture and sensitivity results are known. They should be continued for at least 1 week following CSF sterilization.

Cerebrovascular accidents (CVAs) can be divided into ischemic and hemorrhagic. Approximately 80 to 85% of CVAs are ischemic, 15 to 20% are hemorrhagic.

Of patients presenting with focal deficit, 5% of cases are seizure, tumor, or psychogenic in etiology, and 95% vascular. Eighty to 85% of CVAs are attributed to ischemic infarct, whereas only 15 to 20% are from hemorrhage. With the mainstream use of thrombolytic therapy in the management of ischemic infarction, it is important to be familiar with the exclusion criteria used to make decisions regarding their administration. The use of anticoagulants (heparin or Coumadin), and extreme values of serum glucose may exclude a patient from receiving thrombolytic agents. Patients being considered for thrombolytic therapy should have coagulation studies as well as serum glucose screening prior to their administration.

Intracerebral hemorrhage (ICH) accounts for 15 to 20% of strokes. Etiologies of ICH include amyloid angiopathy, trauma, hemorrhagic transformation of an ischemic infarct, tumors, cerebrovascular malformations (cerebral aneurysms, arteriovenous malformations [AVMs], venous malformations, cavernomas, capillary telangiectasias). Several risk factors are associated with ICH: age, gender, race, prior CVA, alcohol consumption and substance abuse, cigarette smoking, and liver dysfunction. Diagnostic laboratory studies may be utilized in both diagnosis and management.

Coagulopathy is identified using PT, INR, PTT, bleeding time, and platelet count. Coagulopathy is treated with FFP and vitamin K (AquaMEPHYTON) and is carefully monitored using coagulation studies every 4 hours until it is corrected.

Phenytoin is the first-line antiseizure medication, and levels are observed as per the above protocol.

Serum and urine electrolytes, serum and urine osmolarity, and urine specific gravity are ordered every 6 hours to screen for SIADH. Serum uric acid may also be a helpful study to rule in the presence of SIADH (serum uric acid is decreased in SIADH).

Many etiologies for subarachnoid hemorrhage (SAH) exist: rupture of intracranial aneurysms (80%), cerebral AVM (5%), spinal AVM, arterial dissection or rupture, vasculitides, tumors, coagulation disorders, dural sinus thrombosis, drugs, sickle cell disease, and pituitary apoplexy. Risk factors include hypertension, use of oral contraceptives, substance abuse, tobacco abuse, alcohol abuse, pregnancy, lumbar puncture, and advanced age. Along with radiologic studies, diagnostic laboratory studies may assist with diagnosis and are essential for management of SAH.

Blood rheology should be optimized using hemodilution; hemoglobin and hematocrit of 10 mg/dL and 30 to 35%, respectively, enhance perfusion when vasospasm is present.

SIADH and cerebral salt wasting may be detected by following serum and urine electrolytes, serum and urine osmolarity, and urine specific gravity.

The brain death examination should be performed by a neurologist or neurosurgeon or, if unavailable, by a medical or surgical intensivist, anesthesiologist, or pediatrician.

The following procedures must be performed sequentially. First, a CT scan of the brain is ordered, then reviewed, and the injury is documented in great detail. Information describing large-size intracranial hemorrhages, massive ischemic strokes with brain shift, multiple hemorrhagic contusions, large extradural or subdural hematomas, diffuse brain edema with absent basal cisterns, fissures and sulci, and pontine hemorrhages with obstructive hydrocephalus are noted to explain the etiology of coma and loss of brainstem reflexes. In the event of a repeatedly normal CT scan examination, CSF could reveal diagnostic findings such as pleocytosis, increased erythrocyte count, or positive Gram’s stain. CSF should be collected for a polymerase chain reaction (PCR) specifically directed toward herpes simplex or rabies. Next, confounding factors must be ruled out; they must be excluded to proceed with a clinical examination to determine brain death.

The diagnosis of brain death cannot be made until hypothermia is excluded; until the core temperature has reached and been maintained above 32°C.

Acid–base abnormalities increase suspicion of intoxication. Respiratory acidosis is associated with opiates, ethanol, barbiturates, and anesthetics. Metabolic acidosis is common in acetaminophen, ethanol, and methanol, as well as ethylene glycol, salicylates, isoniazid, cyanide, cocaine, strychnine, and papaverine. Alcohol has a plasma half-life of 10 mL/hour, and the legal alcohol limit for determination of brain death is 800 to 1500 mg/L

Naloxone and flumazenil may be administered to patients suspected of opiate or benzodiazepine overdose. Patients are observed for at least 4 times the excretion half-life, assuming no half-life prolongation due to additional organ dysfunction, or (if suspicion of a drug intoxification remains high but cannot be identified) the patient should continue to be observed for a period of 2 days for a change in brainstem reflexes and motor response.

The presence of serum pentobarbital levels in patients with traumatic brain injury may be confusing when attempting to diagnose brain death. Barbiturates have been used in these patients to reduce increased intracranial pressure. Again, it is assumed that the clinical diagnosis of brain death can be made if the serum levels are less than the therapeutic range (less than 5 μg/mL).