Author Credentials and Financial Disclosure: Daniel K. Mullin, MD, is a Clinical Instructor of Emergency Medicine at Drexel University College of Medicine in Philadelphia.
Dr. Mullin has disclosed that he has no financial interests in or relationships with any commercial companies pertaining to this educational activity.
Learning Objectives: After reading this article, the physician should be able to:
- Discuss the usefulness or uselessness of nesiritide to treat acutely decompensated congestive heart failure.
- Identify the essential components of appropriate wound care for prevention of infection and optimal cosmetic outcome.
- Summarize the CDC guidelines for appropriate tetanus vaccinations.
Release Date: September 2007
Intravenous Nesiritide vs. Nitroglycerin for Treatment of Decompensated Congestive Heart Failure: A Randomized Controlled Trial
Young JB, Publication Committee for the VMAC Investigators
Decompensated congestive heart failure is a major cause of morbidity and mortality in the United States, and is the leading hospital discharge diagnosis in patients over 65. But despite its enormous burden on human life and health care economics, no new intravenous agents for acutely decompensated heart failure were approved for use until the arrival of nesiritide. A recombinant human brain, or B-type, natriuretic peptide that has venous, arterial, and coronary vasodilatory properties, nesiritide appears to reduce preload and afterload, and increases cardiac output without direct inotropic effects.
This study was a randomized controlled trial, done to compare the efficacy and safety of intravenous nesiritide, intravenous nitroglycerin, and placebo. The primary endpoints of interest were changes in pulmonary capillary wedge pressure (PCWP) and the patient's self-evaluation of dyspnea from baseline to three hours after the start of the study drug.
The protocol allowed for the use of standard care agents prior to the study drug. There were 489 patients randomized to one of three groups: nesiritide, nitroglycerin, or placebo. Of these 489 patients, 246 had a right heart catheter placed prior to randomization based on each individual investigator's clinical decision.
There appeared to be a statistically significant improvement in PCWP from baseline to three hours in the nesiritide group, as compared with the nitroglycerin and placebo groups. Additionally, the patient's self-assessment of dyspnea was significantly improved in the nesiritide group compared with placebo. There was no difference, however, in patients' self-assessment of dyspnea in the nesiritide group when compared with nitroglycerin. In other words, nesiritide and nitroglycerin were equal in treating symptoms.
The authors noted that adverse events were more common in the nitroglycerin group, mostly consisting of increased benign headaches. There were no significant differences in the frequency or severity of ischemic events, asymptomatic or symptomatic hypotension, or arrhythmias between the nitroglycerin and nesiritide groups in the first 24 hours. Through seven days, deaths occurred in one nitroglycerin and four nesiritide patients. The authors noted that none of these deaths was believed to be due to either study drug. This trial led the authors to conclude that nesiritide, in addition to diuretics, is a useful addition to the initial therapy of patients with acutely decompensated CHF.
Comment: As most physicians already know, a lot of controversy had been stirred up about nesiritide since the publication of this article. First, there were major problems with this particular study. While they stated that the dosing and titration of nitroglycerin was left to the discretion of the investigators and done so in dosing ranges recommended by current guidelines, many physicians believe the doses were too low to be fully effective. While the mean doses in the VMAC trial at three hours were 42 mcg/min in the catheterized group and 29 in the non-catheterized group, many experienced physicians start with doses of 40–50 mcg/min and titrate up quickly to effect (relief of dyspnea) and may reach doses of 150 mcg/min. Results of the trial may have been quite different had nitroglycerin been used more aggressively as usually done in clinical practice.
Another limitation of the study was the fact that the surrogate marker PCWP was one of the primary endpoints. What physicians really care about is lessening symptoms, length of hospital stay, cost, and mortality. The VMAC trial failed to demonstrate any of these.
While beyond the scope of this paper, nesiritide also has been demonstrated to worsen renal function (Circulation 2005;111:1487) and increase mortality (JAMA 2005;293:1900). This led to famed cardiologist Eric Topol's article, “Nesiritide-Not Verified” (New Engl J Med 2005;353:113), where he blasted the FDA for approving nesiritide and the pharmaceutical company for distorting the evidence. “In my view, nesiritide has not yet met the minimal criteria for safety and efficacy. … There will be questions about the appropriateness of … the drug's use or even commercial availability,” Dr. Topol wrote. I'll let the readers make their own opinions.
Hollander JE, Singer AJ
Ann Emer Med 1999;34(3):356
Lacerations occur predominantly in young adults, more commonly in men. The majority of lacerations are on the head and neck (50%) or an upper extremity (35%). The most common mechanism of injury resulting in a laceration is blunt force, such as bumping one's head against a steering wheel.
When evaluating a patient who has sustained a laceration, it is important for the physician to identify conditions that place the patient at risk for infection or delayed healing after wound closure. Diabetes, obesity, malnutrition, chronic kidney disease, old age, and the chronic use of steroids all lead to higher wound infection rates. All of these factors plus the use of chemotherapeutic or immunosuppressive agents delay wound healing.
While evaluating the patient, start with a neurovascular assessment of pulses, motor function, and sensation distal to the laceration. Next examine the wound with maximal lighting in as bloodless a field as possible to search for foreign bodies and tendon lacerations and to fully assess wound depth. At times, anesthesia of the laceration is required to complete an adequate evaluation. Cursory exams of wounds can only lead to trouble. Failure to diagnose foreign bodies is the fifth leading cause of litigation against emergency physicians. Other common wound-related causes of litigation include the development of wound infections and missed injuries to tendons and nerves.
During the history and physical, tetanus immunization status should be verified. If the patient has had the three-dose primary tetanus vaccination series (likely as a child), then the tetanus immune globulin (TIG) is not necessary. He does need the tetanus-diphtheria toxoid (Td) if the last vaccination was five to 10 years prior and the wound is contaminated and if the last vaccination was greater than 10 years ago, regardless of the wound characteristics. If the patient has received less than the primary three doses or if the immunization status is unknown and the wound is likely contaminated, then TD and TIG need to be given simultaneously in the emergency department in different anatomical locations.
When local anesthesia is needed, lidocaine tends to be the most commonly administered agent, but bupivacaine is also popular, given its virtual identical onset of action but longer duration of action. Lidocaine and bupivacaine should be safe in patients with allergies to procaine because they are amide anesthetics while procaine is part of the ester class. Patients are rarely allergic to lidocaine, but when they are, they are usually allergic to methylparaben, used as a preservative in the multi-dose vials. One alternative is single-dose lidocaine (cardiac lidocaine), which does not contain a preservative. Another option is to use a completely different class of anesthetic, usually diphenhydramine.
Local anesthesia can be achieved by several routes: local infiltration, regional application, and topical application. When infiltrating tissue with a local anesthetic, there are several techniques that have been demonstrated to reduce the pain of injection. These include buffering with sodium bicarbonate in a 1:10 ratio, warming the anesthetic to body temperature prior to use, slowing the rate of injection, using smaller needles (25 gauge or smaller), using subcutaneous rather than intradermal injection, and using a topical anesthetic prior to injection. When dealing with a large wound, it is important to remember the maximal allowed dosages of the anesthetic. The maximal safe dose of lidocaine is 4.5 mg/kg, and 7 mg/kg when mixed with epinephrine.
After anesthetizing the wound, the next step is surgical debridement of any crushed or devitalized tissue. This step is absolutely essential for proper wound healing. Removal of hair surrounding a laceration helps with meticulous wound closure, but should be done with clippers rather than a razor. Eyebrow hair should be left alone. All wounds, except for clean face wounds, should be irrigated under high pressure. Adequate high-pressure irrigation can be done easily with a 60 ml syringe and a splash shield. While not discussed in this article, irrigation in a sink with tap water appears to result in equal wound infection rates when compared with high-pressure irrigation with sterile normal saline. (Acad Emerg Med 2007;14:404.)
Most wounds should be closed primarily to reduce patient discomfort and speed healing. There are, however, circumstances when primary closure is not in the patient's best interest. In these instances, the patient should be told to return in three to five days for delayed primary closure. There is a lot of controversy over the amount of time a wound can be safely closed primarily for wound infection rates and eventual wound cosmesis, but it appears to be longer on the face (up to 24 hours in some circumstances) and shorter on the extremities (six to 12 hours).
Sutures are the most commonly used wound closure technique, although tissue adhesives have become quite popular in the proper setting. Most closures in the emergency department require only closure of the skin where the nonabsorbable sutures are used most commonly. Polypropylene (Prolene) has the best tensile strength and the least tissue reactivity, but is the hardest to work with and has the least knot security. Meanwhile silk is the easiest to work with and has the best knot security, but it has the least tensile strength and most tissue reactivity. Nylon (Ethilon) sutures run somewhere in between the two. Deep sutures are occasionally helpful in relieving skin tension, decreasing dead space and hematoma formation, and likely improving cosmetic outcomes. When placing deep sutures, absorbable sutures obviously should be used.
Staples are occasionally the preferred wound closure technique because they can be applied more rapidly than sutures, and appear to be associated with a lower rate of foreign body reaction and infection. Staples are particularly useful for scalp, trunk, and extremity wounds and when saving time is essential.
Tissue adhesives, of which 2-octylcyanoacylate (Dermabond) is the only one employed in the United States, are useful in circumstances where 5-0 sutures or smaller would be appropriate (the face) and skin edges can be held together without an excess of tension. When applying 2-octylcyanoacylate, the wound first should be cleaned appropriately and then manually approximated. Then the clinician should apply at least three to four coats to provide adequate strength. Care should be taken not to get any of the tissue adhesive into the wound. Once applied and dried, the tissue adhesive usually sloughs off in seven to 10 days. When application of tissue adhesives results in suboptimal wound closure and must be removed, antibiotic ointment, petroleum jelly, or acetone is usually helpful.
After a wound has been sutured or stapled, it should be covered with a protective nonadherent dressing for at least 24 hours to allow for adequate epithelization. Maintenance of a moist wound environment has been shown to speed the rate of re-epithelization. Topical antibiotic ointments may help reduce infection rates and prevent scab formation, but should not be applied to wounds after topical adhesives have been used. The routine use of prophylactic antibiotics is not recommended. In general, decontamination is far more important than antibiotics.
About the LLSA
As part of its continuous certification program, the American Board of Emergency Medicine has developed the Lifelong Learning and Self-Assessment (LLSA) program to promote continuous education of diplomates. Each year, beginning in 2004, 16 to 20 articles are chosen based on the Emergency Medicine Model. A list of these articles can be found on the ABEM web site, www.abem.org.
ABEM is not authorized to confer CME credit for the successful completion of the LLSA test, but it has no objection to physicians participating in such activities. EMN's CME activity, Learning to Live with the LLSA, is not affiliated with ABEM's LLSA program, and reading this article and completing the quiz does not count toward ABEM certification. Rather, participants may earn 1 CME credit from the Lippincott Continuing Medical Education Institute, Inc., for each completed EMN quiz.