Control of Chronic Pain and Acute Pain/Hemoglobinopathies

Educational Objectives

The goals of this program are to improve management of opioid administration and the use of peripheral catheters for pain control, and to provide an overview of the most common hemoglobinopathies and coagulopathies. After hearing and assimilating this program, the clinician will be better able to:

1.   Describe the action and effects of opiates.

2.   Recognize the differences between addiction, dependence, and tolerance.

3.   Develop a treatment plan for prescribing opiates, including mutually agreed upon treatment goals and regular monitoring of the patient for compliance and side effects.

4.   Discuss the advantages of using peripheral nerve catheters for management of acute pain .

5.   List the most common hemoglobinopathies and coagulopathies, including sickle-cell disease and von Wille­brand’s disease.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and the planning committee re­ported nothing to disclose.

Acknowledgements

Drs. Dews and Ritzman spoke at the Comprehensive Anesthesiology Review, held March 28 to April 2, 2009, in Cleveland, OH, and sponsored by the Cleveland Clinic Anesthesiology Institute. Dr. Tetzlaff was recorded at Survey of Current Issues in Surgical Anesthesia, held November 15-19, 2008, in Daytona Beach, FL, and sponsored by the Cleveland Clinic Anes­thesiology Institute. The Audio-Digest Foundation thanks the speakers and the Cleveland Clinic Anesthesiology Institute for their cooperation in the production of this program.

Opiates for Chronic Pain

Teresa Dews, MD, Clinical Associate Professor of Anesthesiology, Cleveland Clinic Lerner College of Medi­cine of Case Western Reserve University, and Vice-Chair, Department of Pain Management, Cleveland Clinic, Cleveland, OH

Opioids: natural, semisynthetic, or synthetic derivatives of mu receptor agonists; main effect analgesia; dull pain af­fected more than sharp, except at extremely high doses; also affects limbic system to change emotional response to pain; euphoria or dysphoria possible; may provide anxiolysis; pure mu agonists do not have ceiling effect for analgesia; metabolites of medications may vary effects; morphine  —standard by which other opioids measured

Half-life: varies with agent; short half-lives  —  2 to 4 hr; longer half-lives provide more consistent pain relief, but associated with more side effects and sedation

Metabolism: occurs in liver; influenced by genetic differences or other medications; associated with variations in analgesia and side effects; some patients lack appropriate metabolizing enzymes and may derive no benefit from drugs; active metabolites can influence side effect profile; excreted through kidneys

Side effects: miosis, sedation, mental clouding, vasodilation, constipation, and nausea and vomiting; hyperalgesia (at high doses or spinal administration); long-term use associated with hypogonadism (diminished libido and sexual dysfunction) and reduced cellular immunity

Indications: severe or intractable pain; standard of care for acute or cancer pain; contraindications  —  opiate allergy; active addictive disorder; addictive disorder in remission (relative contraindication)

Drug abuse: 7% to 12% of patients visiting doctors actively abusing >1 agent; incidence estimated at 3 times higher among pain patients; clinician should consider dangers to society as well as patient’s needs; be aware of other in­dividuals in patient’s home who might have access to and appropriate their drugs; some physicians naive about patient’s motives; rare physicians may have their own addictions and abuse their access to drugs; patients may re­sort to doctor-shopping, online pharmacies, or stealing

Addiction: primary chronic neurobiologic disease; development influenced by genetic, psychosocial, and environ­mental factors; characteristic behaviors include impaired control over drug use, compulsive use, continued use despite adverse consequences, and craving for and obsession with drug; euphoria activates nucleus accumbens; inactivates control function of frontal cortex; most addicts abuse drug before developing compulsive behaviors; addictive potential depends on nature of administration, as well as strength of mu receptor activation; pseudoaddiction  —  addictive behaviors exhibited without physiologic addiction; confirmation of true addiction possible only by observing whether higher doses extinguish maladaptive behaviors; risk factors include personal or family history of chemical dependency; drug effects unpredictable

Physical dependence: state of physical adaptation; class-specific syndrome (patient exhibits withdrawal symptoms when drug abruptly discontinued, blood levels drop, or antagonist administered)

Tolerance: adaptive state in which drug effect diminishes with continuing use over time; biologic mechanism un­known; most patients can stabilize at single dose; continuing nociception can counteract development of toler­ance; signs of withdrawal do not always indicate addiction; could suggest missed dose or increased opiate metabolism due to coadministration of another agent

Pain prescriptions: requires patient evaluation and diagnosis, treatment plan, and informed consent that includes dis­cussion of long-term treatment, side effects, and agreement on prescription parameters; re-evaluate patient peri­odically to ensure compliance and attainment of treatment goals; good documentation important for assessing pain relief, adherence, and need for ongoing treatment

Risk-benefit assessment: should determine whether pain responds to opioids; patient diagnosis; presence of other risks; clear treatment goals for clinician and patient; mix different treatment modalities; try conservative mea­sures first, adding opioids if pain moderate to severe; consider psychosocial factors that may influence pain (eg, anxiety disorders, history of depression, attention-deficit/hyperactivity disorder); evaluate patient’s risk; use screening tools; if concerned that someone else in household may take drugs, find another way to manage pa­tient’s pain; become familiar with urine toxicology and available assays

Titration: use sustained-release medication whenever possible; allow serum levels to equilibrate before changing dose (minimizes side effects); sustained-release preparations improve compliance, decrease potential for abuse and addiction, and provide consistent blood levels of drug

Red flags: repeated claims of loss of prescription or medications; requests for early refills; increasing dose without clinician’s permission; some states have websites showing whether patient receives prescriptions from multiple physicians

Peripheral Nerve Catheters for Acute Pain Control

John E. Tetzlaff, MD, Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine of Case West­ern Reserve University, and Program Director, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH

Axillary catheter: in comparison of continuous and intermittent injection of dilute bupivacaine for postoperative pain control after microsurgery, both groups experienced excellent analgesia, but 24-hr blood levels higher with continuous infusion; authors questioned efficacy of technique for mild to moderate postoperative pain; other au­thors used intermittent infusion of 1% mepivacaine during finger reimplantation; no central nervous system toxicity noted; highest level achieved 7 µg/dL (lower than toxicity of lidocaine); catheters may be difficult to maintain; good results with distal placement (»4 cm below axillary crease); surgical anesthesia excellent, with little difficulty maintaining catheter for 24 to 48 hr postoperatively; other authors obtained good pain control with axillary cathe­ters after shoulder surgery

Interscalene catheters: in 1989 study of 24 patients, 6 experienced catheter failure; of remaining 18, 4 had catheter displacement; complications included local anesthetic toxicity (2 patients), hoarseness, and motor block; results better in 1993 study of patients undergoing shoulder surgery; received 0.75% bupivacaine intraoperatively, 0.125% bupivacaine continuously thereafter; 100% diaphragmatic impairment observed during surgery and 24 hr postoper­atively; rate of catheter failure 10%; authors speculated technique associated with 100% impairment of ipsilateral phrenic nerve; in 1997 study comparing with patient-controlled analgesia (PCA) after open shoulder surgery, cath­eter associated with better pain control, less nausea and pruritus, and greater patient satisfaction; however, 2 of 20 catheters failed; in 2000 study of patients using catheters at home, success rate 100%, with good pain control and no complications; of 60 patients in another study, good pain control reported, but 30 developed kinked catheters; substantial incidence of motor block; authors recommended continuous infusion plus demand

Femoral catheters: in 1999 comparison between PCA and epidural catheters following knee surgery, associated with fewest complications; similar findings obtained in 1991 study; complications recorded in 2001 study of 211 pa­tients undergoing 48-hr catheterization; no infections observed, but bacteria cultured from 57% of catheter tips (possibly due to contamination by skin organisms upon removal); in 1996 comparison of catheter alone with cathe­ter plus single-injection subgluteal sciatic nerve block after knee surgery, addition of sciatic injection associated with better control of severe pain after knee replacement for first 24 hr, no difference thereafter; authors recom­mended sciatic injection for acute pain control; less urgent for anterior cruciate ligament reconstruction, which oc­curs at or above joint; other investigators reported good results with fascia iliaca block (modification of lumbar plexus block) in hip replacements; catheter placed under fascia iliaca using “double-pop” technique

Sciatic catheters: in 2002 study of patients undergoing foot and ankle surgery, subgluteal placement associated with good pain control; failures with transgluteal approach due to lack of distinct sheath around sciatic nerve; results better when catheter stylet modified; 30 patients underwent popliteal sciatic block; patients discharged to home with catheter; excellent analgesia with ropivacaine; 3 catheters dislodged and 1 pump failed; 30% of patients made ³1 off-hours call to physician for assistance with pump or catheter

Conclusions: nerve block between wound and central nervous system “single best way to achieve pain control”; catheter effective until patient ready for oral medication; analgesia excellent and patient satisfaction high; compli­cations minimal and justified by superior pain control

Hemoglobinopathies and Disorders of Coagulation

Stacy Ritzman, MD, Staff Anesthesiologist, Cleveland Clinic Foundation, Cleveland, OH

Sickle cell disease: most common hemoglobinopathy in United States; 8% to 10% of black Americans carry trait (heterozygous);  0.2% have disease (homozygous); in homozygotes, abnormal hemoglobin aggregates and po­lymerizes when exposed to low oxygen tensions (pO₂ <40 mm Hg); sickled red blood cells lead to microvascular occlusion, tissue ischemia, and infarction; red blood cells also adhere to endothelium, thereby activating coagula­tion system and inflammatory mediators; life span of red blood cells 12 to 17 days (normal, 120 days); diagnosed by hemoglobin electrophoresis

Crises: vaso-occlusive (sickle cell) crisis  —  sickling and microvascular occlusion; patients present with pain; treated with analgesics and by correcting underlying cause of sickling; splenic sequestration  —  red blood cell trapping in spleen, causing precipitous anemia; presenting symptoms are left upper quadrant pain, and some­times hypovolemic shock; treated with intravenous (IV) fluids and transfusion; aplastic crisis  —  failure of reticu­locytosis due to bone marrow suppression; signs and symptoms related to severe anemia; treated with transfusion; acute chest syndrome  —  medical emergency; most common cause of death in sickle cell patients; caused by deoxygenation or sickling within pulmonary vasculature; diagnosed by new pulmonary infiltrate on chest x-rays, combined with chest pain, fever, tachypnea, wheezing, hypoxemia, or increased work of breathing; patients develop progressive pulmonary fibrosis and hypertension, and chronic respiratory insufficiency

Management of surgical patients: avoid anything that promotes sickling; maintain hematocrit >30%; avoid exces­sive oxygen consumption and ensure adequate oxygenation; hydrate well to avoid vascular stasis; maintain nor­mothermia; avoid acidosis; risk for perioperative pulmonary complications 10 times higher than in general population

Thalassemia: caused by insufficient production of hemoglobin polypeptide chain; 4 types (major, minor, and a tha­lessemias); clinical manifestations  —  anemia, hemolytic effects, and bone marrow hyperplasia; can cause facial dysmorphism due to maxillary overgrowth and extramedullary marrow formation, mostly in vertebral column and pleural space; considerations  —  after multiple transfusions, patients may develop cardiac dysfunction from hemo­siderosis; facial bone hyperplasia may interfere with intubation; epidural, spinal, and intrapleural anesthesia rela­tively contraindicated due to extramedullary marrow

Methemoglobinemia: caused by oxidation of heme iron from ferrous to ferric state (unable to bind oxygen); patients cyanotic despite normal pO₂; diagnosed by arterial blood gas co-oximetry; methemoglobin absorbs red and infrared light in 1 to 1 ratio, corresponding to 85% saturation; cyanosis develops at 50% methemoglobin concentration; 70% concentration fatal; treatment  —  methylene blue in dose of 1 mg/kg over 5 min, repeated every 60 min if cya­nosis persists; doses >7 mg/kg may oxidize hemoglobin to methemoglobin and exacerbate symptoms

Carboxyhemoglobinemia: caused by exposure to carbon monoxide, which competes with oxygen for hemoglobin; affinity 200 to 250 times greater than that of oxygen; wide range of signs and symptoms; concentrations >60% le­thal; no symptoms if concentration <10%; diagnosed on direct co-oximetry; pO₂ normal; treat with 100% oxygen

Von Willebrand’s disease: most common hereditary coagulopathy; most patients unaware of disease until they expe­rience perioperative complications; von Willebrand factor made by endothelial cells and megakaryocytes, and has roles in hemostasis; 3 subtypes; type 1 most common; type 3 rare (absence of factor); patients usually have history of mucocutaneous bleeding; also have low factor VIII levels and prolonged bleeding time; treatment options in­clude desmopressin acetate (DDAVP), 0.3 µg/kg intravenously, for types 1 and 2A (contraindicated in type 2B); maximal effect seen within 30 min; repeat every 12 to 24 hr; tachyphylaxis develops eventually; add antifibrinolytic agent because treatment increases tissue plasminogen activator; other treatment options include plasma concen­trates; von Willebrand factor levels of 80% to 100% desirable for major surgery, with postoperative levels at 40% for 3 to 10 days

Hemophilia: hemophilia A  —  most common; caused by deficiency of factor VIII; affects 1 in 10,000 males; causes deep tissue bleeding with hemarthrosis, hematuria, or soft tissue hematomas; mild  —  factor VIII levels 5% to 30% of normal; moderate  —  1% to 5% of normal; severe  —  <1% of normal; most common form; patients frequently bleed spontaneously; levels of von Willebrand factor normal; treatment options include DDAVP, plasma-derived concentrates (factor VIII concentrate most effective); consider plasma volume and desired procoagulant activity when calculating amount of factor VIII to replace; for elective surgery, correct to 50% to 100%; hemophilia B  —  defective factor IX; second most common; must be diagnosed by findings of deficient factor IX and normal factor VIII

Disseminated intravascular coagulation: caused by circulating tissue factor, which leads to uncontrolled clot for­mation, microvascular thrombosis, tissue ischemia, and multiple organ system failure, as well as severe bleeding; treat by managing underlying condition

Suggested Reading

Capdevila X et al: Continuous psoas compartment block for postoperative analgesia after total hip arthroplasty: new land­marks, technical guidelines, and clinical evaluation. Anesth Analg 94:1606, 2002; Dews TE, Mekhail N: Safe use of opi­oids in chronic noncancer pain. Cleve Clin J Med 71:897, 2004; Fine PG et al: Long-acting opioids and short-acting opioids: appropriate use in chronic pain management. Pain Med 10 Suppl 2:S79, 2009; Firth PG: Anesthesia and  hemo­globinopathies. Anesthesiol Clin 27:321, 2009; Goodwin SR et al: Sickle cell and anesthesia: do not abandon well-estab­lished practices without evidence. Anesthesiology 103:205, 2005; Heitz JW et al: New and emerging analgesics and analgesic technologies for acute pain management. Curr Opin Anaesthesiol July 31, 2009 [Epub ahead of print]; Kang SB et al: Continuous axillary brachial plexus analgesia in a patient with severe hemophilia. J Clin Anesth 15:38, 2003; Liu SS, Salinas FV: Continuous plexus and peripheral nerve blocks for postoperative analgesia. Anesth Analg 96:263, 2003; Rawal N et al: Patient-controlled regional analgesia (PCRA) at home: controlled comparison between bupivacaine and ropivacaine brachial plexus analgesia. Anesthesiology 96:1290, 2002; Rawal N: Postoperative pain treatment for ambulatory surgery. Best Pract Res Clin Anaesthesiol 21:129, 2007; Reich A, Szepietowski JC: Opioid-induced pruritus: an update. Clin Exp Dermatol July 29, 2009 [Epub ahead of print]; Riley III JL et al: Cognitive-affective and somatic side effects of morphine and pentazocine: side-effect profiles in healthy adults. Pain Med August 7, 2009 [Epub ahead of print].