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Thursday, July 5, 2012

Ventricular septal defect

VENTRICULAR SEPTAL DEFECTS

Essentials of Diagnosis

History of murmur appearing shortly after birth.
Holosystolic murmur at left sternal border radiating rightward.
Left atrial and LV or biventricular enlargement.
High-velocity color-flow Doppler jet across VSD.
Increased pulmonary flow velocities.

General Considerations

Because of the tendency for many VSDs to close spontaneously (see later discussion) and the tendency of larger defects to appear in early childhood as CHF, it is relatively uncommon to encounter adults with previously undiagnosed VSDs of hemodynamic consequence. Ventricular septal defects in adults are usually either small and hemodynamically insignificant or large and associated with Eisenmenger syndrome. The importance of identifying the former is that they pose an ongoing risk of endocarditis and the potential complication of progressive aortic regurgitation. Eisenmenger syndrome is discussed later in this chapter.

Classifications of VSDs can be based on anatomic location or physiology. The anatomic classification includes defects of both the membranous and muscular portions of the ventricular septum (Figure 28–10). Membranous VSDs can be subdivided into supracristal (also known as doubly committed subarterial), perimembranous (the inlet portion of the membranous septum), and malalignment (found in TOF with an overriding aorta) defects. The muscular VSDs, often multiple, may be located in the inlet or outlet regions or within the trabecular portion of the septum. Classifying VSDs physiologically is based on the size of the defect as well as the relative vascular resistances within the systemic and pulmonary circulation. A high-pressure gradient exists across a small restrictive VSD, with normal or mildly elevated pulmonary artery pressure and predominant left-to-right shunting. A large nonrestrictive VSD permits equalization of RV and LV pressures with obligatory pulmonary hypertension (in the absence of RV outflow-tract obstruction) and bidirectional shunting. The smallest VSD (maladie de Roger) is characterized by a hemodynamically insignificant shunt, a loud murmur, and an intermediate-to-high risk of endocarditis.

In the infant, left-to-right shunting occurs only when PVR falls below systemic vascular resistance, and the murmur usually becomes audible in the first month of life. With a large nonrestrictive defect, PVR may not fall; if the defect is not surgically closed by age 2, irreversible pulmonary hypertension may ensue. The volume overload caused by a large restrictive VSD may cause CHF in the first 6 months of life. Approximately 40% of VSDs close spontaneously by age 3, and a smaller percentage close before age 10. Generally, the smaller defects are more likely to close, but even in infants with heart failure, 7% will experience spontaneous closure.

Three late complications of VSD are worth mentioning. Tricuspid regurgitation may rarely result when the septal leaflet of the tricuspid valve is deformed by the ventricular septal aneurysm that causes spontaneous closure of a perimembranous VSD. Aortic regurgitation is common in patients with doubly committed subarterial VSDs (supracristal, or outlet, VSDs), as a result of herniation of the right aortic sinus into the defect; it also occurs in those with perimembranous VSDs. Infundibular PS from hypertrophy of the RV outflow tract can develop, functionally dividing the RV into inflow and outflow segments, a condition termed "double-chambered right ventricle." If a sufficient pressure gradient develops, RV systolic pressure can exceed LV systolic pressure and right-to-left shunting can occur across the VSD. The resultant hypoxia may only occur during exercise.

Clinical Findings

SYMPTOMS AND SIGNS

The young adult with an uncorrected VSD and normal pulmonary artery pressures is usually asymptomatic, with normal or minimally diminished exercise tolerance. Like those with ASDs, exertional dyspnea often develops in patients with VSDs after the age of 30 when the Q_p:Q_s exceeds 2–3:1. Individuals with smaller shunts rarely report symptoms. The most disabled group with pulmonary hypertension and cyanosis (Eisenmenger physiology, or syndrome) will be discussed later.

Physical findings depend on the size of the VSD. The patient with uncomplicated VSD is acyanotic, and the LV apical impulse is displaced laterally and may be hyperdynamic. A holosystolic murmur occurs, often associated with a systolic thrill, heard best in the fourth or fifth intercostal space along the left sternal border, with radiation to the right parasternal region. Because of the increased flow across the mitral valve, an S₃ gallop and a diastolic rumble may be present. Additional signs of tricuspid insufficiency (prominent jugular venous v wave and systolic murmur) or aortic valve regurgitation (diastolic blowing murmur, increased arterial pulses) will be present in patients with these complications.

DIAGNOSTIC STUDIES

Electrocardiography and Chest Radiography

In the presence of a large shunt, the ECG is suggestive of LVH or biventricular hypertrophy, with biphasic QRS complexes in the transitional precordial leads. Evidence of left or right atrial enlargement is present in only about 25% of patients.

Cardiac enlargement with an increased cardiac silhouette is evident on chest radiograph only in the presence of a large left-to-right shunt. In the absence of pulmonary hypertension, there is evidence of pulmonary vascular engorgement with a plethora of the peripheral vasculature as well as enlargement of the proximal vessels. Left atrial enlargement may be evident on the lateral chest radiograph.

It is important to remember that in most adults with a small VSD (< 1.5–2:1 shunt), both the ECG and radiograph are normal, even in the presence of a loud murmur. On the other hand, the presence of pulmonary hypertension alters the ECG and radiograph findings.

Echocardiography

Two-dimensional and Doppler echocardiography can usually define the location and often the size of a VSD, although accurate Doppler shunt quantitation may not be possible in the adult. There is evidence of left atrial and LV dilatation. The right-heart chamber dimensions are usually normal, although the main pulmonary artery may appear dilated. The presence of RVH usually signifies pulmonary hypertension or associated PS (with right-to-left shunting and cyanosis). Usually only the largest defects, often located in the membranous septum, can actually be visualized echocardiographically (Figure 28–11). The aneurysmal pouch of a ventricular septal aneurysm may be seen in the parasternal short-axis view just below the aortic valve in the inlet portion of the septum near the septal leaflet of the tricuspid valve. Saline contrast administration shows a negative contrast effect within the RV, and a small degree of bidirectional shunting is sometimes present, with microbubbles appearing in the LV.

In continuous wave Doppler, the peak velocity of the jet across the ventricular septum provides the peak systolic LV-RV gradient (using the modified Bernoulli equation). Subtracting this gradient from the systolic blood pressure gives the peak RV systolic pressure. In the absence of a pressure gradient across the RV outflow tract—including the pulmonary valve (which should be carefully sought)—the RV systolic pressure is equivalent to the pulmonary artery systolic pressure. Additional Doppler evidence of the left-to-right shunt is found in the increased pulmonary artery flow velocity.

In the postrepair patient, the VSD patch may or may not be apparent, depending on the size of the original defect. Once endothelialized, the patch may not cause acoustic shadowing (or distal echo blockout). Color-flow Doppler may demonstrate patch leaks at the peripheral suture lines of the patch in a small percentage of patients. Spontaneous closure of a VSD involving juxtaposed tricuspid valve tissue may cause significant tricuspid regurgitation. Varying degrees of aortic regurgitation may be present and are most often associated with membranous or supracristal VSDs.

Cardiac Catheterization

Although the diagnosis is often made noninvasively, the decision to close a VSD rests on accurate measurements of the shunt ratio and the level of PVR. Catheterization is therefore often necessary for therapeutic decision making.

Right-heart catheterization with sequential measurements of oxygen saturation reveals a step-up within the body of the RV. As with an ASD, the higher the RV oxygen saturation, the greater the degree of shunting. For the calculation of Q_p:Q_s, the same formula is used as for ASD, except that the mixed venous blood sample is drawn from the right atrium. Pulmonary artery pressures and vascular resistance should be measured and a gradient across the RV outflow tract, including the infundibulum and the pulmonary valve, must be excluded. Left ventriculography in the cranial left anterior oblique projection will reveal the location of the defect as contrast enters the RV.

Prognosis & Treatment

As previously mentioned, adults with large, uncorrected VSDs are uncommonly encountered. With an uncorrected VSD, the overall 10-year survival rate after initial presentation is 75%. Survival is adversely affected by functional class greater than New York Heart Association I, cardiomegaly, and elevated pulmonary artery pressure (> 50 mm Hg). As in patients with ASD, surgery is generally recommended when the magnitude of the systemic-to-pulmonary-shunt ratio exceeds 2:1. Other indications for surgery may include recurrent endocarditis and progressive aortic regurgitation.

In patients with small VSDs treated either conservatively or with surgery, outcomes are identical for patients with a Q_p:Q_s < 2.0, normal PVR, no LV volume overload or VSD-related aortic regurgitation, and no symptoms of exercise intolerance.

Surgery for closure of VSDs has been available for more than 40 years, and long-term follow-up data are available. Surgery prior to age 2—even in infants with a large VSD, high pulmonary blood flow, and preoperative pulmonary hypertension—almost always prevents the development of pulmonary vascular obstructive disease. In patients who underwent surgery during the 1960s and 1970s, there is an approximately 20% incidence of residual left-to-right shunt and a persistent risk of endocarditis. Ventricular arrhythmias and RBBB are more common with a repair performed via right ventriculotomy (eg, muscular or subarterial VSD); when possible, the right atrium is the preferred approach. The risk of sudden death and complete heart block is low. Most patients who have VSDs repaired in childhood survive to lead normal adult lives.

Devices have been developed for percutaneous closure of both muscular and perimembranous VSDs but are not yet commercially available in the United States. Initial case series suggest high success rates and low complication rates. Reported complications (in nine patients) include conduction anomalies and aortic or tricuspid regurgitation. More extensive follow-up data are needed before device implantation becomes routine.

Gabriel HM et al. Long-term outcome of patients with ventricular septal defect considered not to require surgical closure during childhood. J Am Coll Cardiol. 2002 Mar 20;39(6):1066–71. [PMID: 11897452]

Minette MS et al. Ventricular septal defects. Circulation. 2006 Nov 14;114(20):2190–7. [PMID: 17101870]

Wednesday, July 4, 2012

Sepsis and septic shock

The systemic inflammatory response to infection, termed sepsis, is not unique to severe infections because similar manifestations may be encountered with noninfectious illnesses. Moreover, it does not necessarily indicate the presence of bacteremia. The use of the term SIRS has been suggested by the Society of Critical Care Medicine (SCCM), European Society of Intensive Care Medicine (ESICM), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), and Surgical Infection Society (SIS). The SCCM/ESICM/ACCP/ATS/SIS conference introduced the concept of predisposition, insult infection, response, organ dysfunction (PIRO) to classify sepsis. Severe sepsis exists when the response is associated with organ dysfunction. The term MODS has been suggested to describe progressive dysfunction of two or more organs that is associated with sepsis. Septic shock is defined as acute circulatory failure—systolic blood pressure < 90 mm Hg, mean arterial pressure < 60 mm Hg, or a 40 mm Hg reduction in systolic blood pressure from baseline despite adequate volume resuscitation—in a patient with sepsis.

PATHOPHYSIOLOGY OF SIRS

A mild systemic inflammatory response to any bodily insult may normally have some salutatory effects. However, a marked or prolonged response, such as that associated with severe infections, is often deleterious and can result in widespread organ dysfunction. Although gram-negative organisms account for a majority of infection-related SIRS, many other infectious agents are capable of inducing the same syndrome. These organisms either elaborate toxins or stimulate release of substances that trigger this response. The most commonly recognized initiators are the lipopolysaccharides (LPSs), which are released by gram-negative bacteria. LPS is composed of an O polysaccharide, a core, and lipid A. The O polysaccharide distinguishes between different types of gram-negative bacteria, whereas lipid A, an endotoxin, is responsible for the compound's toxicity. The resulting response to endotoxin involves a complex interaction between macrophages/monocytes, neutrophils, lymphocytes, platelets, and endothelial cells that can affect nearly every organ.

The central mechanism in initiating SIRS appears to be the abnormal secretion of cytokines. These low-molecular-weight peptides and glycoproteins function as intercellular mediators and normally regulate many biological processes, including local and systemic immune responses, inflammation, wound healing, and hematopoiesis. The most important cytokines released during SIRS are IL-6, adrenomedullin, soluble (s)CD₁₄, sELAM-1, MIP-1

, extracellular phospholipase A₂, and C-reactive protein. The resulting inflammatory response involves release of potentially harmful phospholipids, attraction of neutrophils, and activation of the complement, kinin, and coagulation cascades.

Increased phospholipase A₂ levels release arachidonic acid from cell membrane phospholipids. Cyclooxygenase converts arachidonic acid to thromboxane and [dx id=""]prostaglandins[/dx], whereas lipoxygenase converts arachidonic acid into leukotrienes (slow-reacting substances of anaphylaxis). Increased phospholipase A₂ and acetyltransferase activities result in the formation of another potent proinflammatory compound, platelet-activating factor (PAF). Attraction and activation of neutrophils release a variety of proteases and free radical compounds that damage vascular endothelium. Activation of monocytes causes them to express increased amounts of tissue factor, which in turn can activate both the intrinsic and extrinsic coagulation cascades.

INFECTIONS IN THE ICU

Infections are a leading cause of death in ICUs. Serious infections may be acquired outside the hospital (community acquired) or subsequent to admission for an unrelated illness (nosocomial). The term "nosocomial infection" describes hospital-acquired infections that develop at least 48 h following admission. The reported incidence of nosocomial infections in ICU patients ranges between 10% and 50%. Strains of bacteria resistant to commonly used antibiotics are often responsible. Host immunity plays an important role in determining not only the course of an infection but also the types of organisms that can cause infection. Thus, organisms that normally do not cause serious infections in immunocompetent patients can produce life-threatening infections in those who are immunocompromised

Critically ill patients frequently have demonstrable abnormal host defenses, including defective chemotaxis and phagocytosis, altered helper:suppressor T lymphocyte ratios, and impaired humoral immunity. Other host factors include age, drug therapy, integrity of mucosal and skin barriers, and underlying disease. Thus, advanced age (> 70 years), corticosteroid therapy, chemotherapy, prolonged use of invasive devices, respiratory failure, renal failure, head trauma, and burns are established risk factors for nosocomial infections. Patients with burns involving greater than 40% of body surface area have significantly increased mortality from infections. Use of topical antibiotics such as sodium mafenide, silver sulfadiazine, and nystatin delays but does not prevent wound infections. Early removal of the necrotic eschar followed by skin grafting and wound closure appears to reverse immunological defects and reduce infections.

Most nosocomial infections arise from the endogenous bacterial flora. Furthermore, many critically ill patients eventually become colonized with resistant bacterial strains. The urinary tract accounts for up to 35–40% of nosocomial infections. Urinary infections are usually due to gram-negative organisms and are associated with the use of indwelling catheters or urinary obstruction. Wound infections are the second most common cause, accounting for up to 25–30%, with pneumonia accounting for another 20–25%. Intravascular catheter-related infections are responsible for 5–10% of ICU infections.

Nosocomial pneumonias are usually caused by gram-negative organisms and are the leading cause of death in many ICUs. GI bacterial overgrowth with translocation into the portal circulation and retrograde colonization of the upper airway from the GI tract followed by aspiration are possible mechanisms for entry for these bacteria. Preservation of gastric acidity inhibits overgrowth of gram-negative organisms in the stomach and their migration into the oropharynx. Tracheal intubation does not appear to provide effective protection because patients commonly aspirate gastric fluid containing bacteria in spite of a properly functioning TT cuff; nebulizers and humidifiers can also be sources of infection. Selective decontamination of the gut with nonabsorbable antibiotics may reduce the incidence of infection but does not change outcome.

Wounds are common sources of sepsis in postoperative and trauma patients; limited antibiotic prophylaxis appears to decrease the incidence of postoperative infections in some groups of patients. Although more commonly seen in postoperative patients, intraabdominal infections due to perforated ulcer, diverticulitis, appendicitis, and acalculous cholecystitis can also develop in critically ill nonsurgical patients. Intravascular catheter-related infections are most commonly due to Staphylococcus epidermidis, Staphylococcus aureus, streptococci, Candida species, and gram-negative rods. Bacterial sinusitis may be an unrecognized source of sepsis in nasally intubated patients. The diagnosis is suspected from purulent drainage and confirmed by radiographs and cultures.

SEPTIC SHOCK

The SCCM/ESICM/ACCP/ATS/SIS Consensus Conference defines septic shock as sepsis associated with hypotension (systolic blood pressure < 90 mm Hg, mean arterial pressure < 60 mm Hg, or systemic blood pressure < 40 mm Hg from baseline) despite adequate fluid resuscitation. Septic shock is usually characterized by inadequate tissue perfusion and widespread cellular dysfunction. In contrast to other forms of shock (hypovolemic, cardiogenic, neurogenic, or anaphylactic), cellular dysfunction in septic shock is not necessarily related to the hypoperfusion. Instead, there may be a metabolic block at the cellular level that contributes to impaired cellular oxidation.

Pathophysiology

A severe or protracted SIRS can result in septic shock. Septic shock is most commonly due to gram-negative infections arising from the genitourinary tract or from the lungs in hospitalized patients, but identical presentations are also seen with other pathogens. Bacteremia is usually present but may be absent. Increased nitric oxide levels may be responsible for the vasodilation. The hypotension is also due to a decreased circulating intravascular volume resulting from a diffuse capillary leak. Many patients also manifest evidence of myocardial depression. Activation of platelets and the coagulation cascade can lead to the formation of fibrin-platelet aggregates, which further compromise tissue blood flow. Hypoxemia resulting from ARDS accentuates tissue hypoxia. The release of vasoactive substances, formation of microthrombi in the pulmonary circulation, or both together increase pulmonary vascular resistance.

HEMODYNAMIC SUBSETS

The circulation in patients with septic shock is often described as either hyperdynamic or hypodynamic. In reality, both represent the same process, but their expression depends on preexisting cardiac function and intravascular volume and where the patient is on the spectrum of response. Systemic venodilation and transudation of fluid into tissues result in relative hypovolemia in patients with sepsis.

Hyperdynamic septic shock is characterized by normal or elevated cardiac output and profound vasodilation (low systemic vascular resistance). Decreased myocardial contractility is often demonstrable even in hyperdynamic patients. Mixed venous oxygen saturation is characteristically high in the absence of hypoxemia and likely reflects the high cardiac output and the cellular metabolic defect in oxygen utilization.

Hypodynamic septic shock, usually seen later in the course of shock, is characterized by decreased cardiac output with low or normal systemic vascular resistance. It is more likely to be seen in severely hypovolemic patients and those with underlying cardiac disease. Myocardial depression is a prominent feature. Mixed venous oxygen saturation may be low in these patients. Pulmonary hypertension is also often prominent in septic shock. Elevation of pulmonary vascular resistance widens the normal pulmonary artery diastolic-to-wedge pressure gradient; large gradients have been associated with a higher mortality rate. The increase in pulmonary vascular resistance may contribute to right ventricular dysfunction.

Clinical Manifestations

Manifestations of septic shock appear to be primarily related to host response rather than the infective agent. Septic shock classically presents with an abrupt onset of chills, fever, nausea (and often vomiting), decreased mental status, tachypnea, hypotension, and tachycardia. The patient may appear flushed and feel warm (hyperdynamic) or pale with cool and often cyanotic extremities (hypodynamic); in the latter case, a high index of suspicion is required. In old, debilitated patients and in infants, the diagnosis often is less obvious and hypothermia may be seen.

Leukocytosis with a leftward shift to premature cell forms is typical, but leukopenia can be seen with overwhelming sepsis and is an ominous sign. Progressive metabolic acidosis (usually lactic acidosis) is typically partially compensated by a concomitant respiratory alkalosis. Elevated lactate levels reflect both increased production resulting from poor tissue perfusion and decreased uptake by the liver and kidneys. Hypoxemia may herald the onset of ARDS. Oliguria is most commonly due to the combination of hypovolemia, hypotension, and a systemic inflammatory insult and often progresses to ARF. Elevations in serum aminotransferases and bilirubin are due to hepatic dysfunction. Insulin resistance is uniformly present and produces hyperglycemia. Thrombocytopenia is common and is often an early sign of sepsis. Laboratory evidence of disseminated intravascular coagulation (DIC) is often present but is rarely associated with a bleeding diathesis. The latter responds only to control of the sepsis. Gastric mucosal stress ulceration is common. Respiratory and renal failure are the leading causes of death.

Neutropenic patients (absolute neutrophil count 500/

L) may develop macular or papular lesions that can ulcerate and become gangrenous (ecthyma gangrenosum). These lesions are commonly associated with Pseudomonas septicemia but can be caused by other organisms. Perirectal abscesses can develop very quickly in neutropenic patients with few external signs; patients may complain only of perirectal pain.

Treatment

Septic shock is a medical emergency that requires immediate and aggressive intervention. Treatment is threefold: (1) control and eradication of the infection by appropriate and timely intravenous antibiotics, drainage of abscesses, debridement of necrotic tissues, and removal of infected foreign bodies; (2) maintenance of adequate perfusion with intravenous fluids and inotropic and vasopressor agents; and (3) supportive treatment of complications such as ARDS, ARF, GI bleeding, and DIC.

Antibiotic treatment must be initiated before pathogens are identified but after adequate cultures are obtained (usually of blood, urine, wounds, and sputum). Combination therapy with two or more antibiotics is generally indicated until pathogens are known. In most instances, the combination of a penicillin/

-lactamase inhibitor or third-generation cephalosporin with an aminoglycoside is adequate. Additional diagnostic studies may be indicated (eg, thoracentesis, paracentesis, lumbar puncture, or computed tomographic scans). Debridement and drainage of infections and abscesses should be undertaken expeditiously.

Empiric antibiotic therapy in immunocompromised patients should be based on pathogens that are generally associated with the immune defect. Vancomycin is added if intravascular catheter-related infection is suspected. Clindamycin or metronidazole should be given to neutropenic patients if a rectal abscess is suspected. Many clinicians initiate amphotericin B, fluconazole, or caspofungin therapy for a presumed fungal infection or when an immunocompromised patient continues to experience fever after 96 h of antibiotic therapy. Granulocyte colony-stimulating factor or granulocyte–macrophage colony-stimulating factor may be used to shorten the period of neutropenia; granulocyte transfusion may occasionally be used in refractory gram-negative bacteremia. Diffuse interstitial infiltrates on a chest radiograph may suggest unusual bacterial, parasitic, or viral pathogens; many clinicians initiate empiric therapy with trimethoprim-sulfamethoxazole and erythromycin in such instances. Nodular infiltrates on a radiograph suggest a fungal pneumonia and may warrant antifungal therapy. Antiviral therapy should be considered in septic patients who are more than 1 month post–bone marrow or solid organ transplantation.

Tissue oxygenation and perfusion are maintained with oxygen therapy, intravenous fluids, inotropes, vasopressors and packed red blood cell transfusions to keep hemoglobin levels > 8–10 g/dL. Marked "third spacing" is characteristic of septic shock. An inotrope should be used if intravenous fluids fail to quickly restore adequate perfusion. Colloid solutions more rapidly restore intravascular volume compared with crystalloid solutions but otherwise offer no proven additional benefit. Inotropic therapy is generally initiated if 1–3 L of intravenous fluids do not correct the hypotension. Hematocrit should probably be maintained at or above 24–30% to enhance oxygen delivery. Pulmonary artery catheterization greatly facilitates management in such instances because it allows measurement of PAOP and cardiac output. Most clinicians generally select dopamine as the initial inotrope; others may use dobutamine because it more effectively increases cardiac output and oxygen delivery (Table 49–14). Some studies suggest that patient mortality may be lower if oxygen delivery can be increased. When either dopamine or dobutamine is ineffective in increasing blood pressure and cardiac output, epinephrine (2–18

g/min) is the agent of choice. In patients with refractory hypotension, norepinephrine, vasopressin, or both are administered with a good improvement in blood pressure but without evidence that it affects outcome. Severe acidosis may decrease the efficacy of inotropes and should therefore generally be corrected (pH > 7.20) with bicarbonate therapy in patients with refractory hypotension. Even in the absence of arterial hypotension, "renal" doses of dopamine may help maintain urinary output but have not been shown to improve outcome. The use of corticosteroids, naloxone, opsonins (fibronectin), and monoclonal antibodies directed against lipopolysaccharide in septic shock has been disappointing, but inhibitors of the coagulation cascade show promise. One such agent, activated protein C, drotrecogin alfa, has been approved by the U.S. Food and Drug Administration for use during sepsis. Because of the expense of this agent and questions about long-term outcome, many ICUs have criteria for when it can be administered to patients that are derived from the original study results

What is sunburn sunburns sunburned

A sunburn is a burn to living tissue, such as skin, which is produced by overexposure to ultraviolet (UV) radiation, commonly from the sun's rays. Usually, normal symptoms in humans and other animals consist of red or reddish skin that is hot to the touch, general fatigue, and mild dizziness. An excess of UV radiation can be life-threatening in extreme cases. Exposure of the skin to lesser amounts of UV radiation will often produce a suntan.

Excessive UV radiation is the leading cause of primarily non-malignant skin tumors.^[1]^[2] Sunscreen is widely agreed to prevent sunburn, although some scientists argue that it may not effectively protect against malignant melanoma, which either is caused by a different part of the ultraviolet spectrum or is not caused by sun exposure at all.^[3]^[4] Clothing, including hats, is considered the preferred skin protection method. Moderate sun tanning without burning can also prevent subsequent sunburn, as it increases the amount of melanin, a skin photoprotectant pigment that is the skin's natural defense against overexposure. Importantly, both sunburn and the increase in melanin production are triggered by direct DNA damage. When the skin cells' DNA is damaged by UV radiation, type I cell-death is triggered and the skin is replaced.^[5] Malignant melanoma may occur as a result of indirect DNA damage if the damage is not properly repaired. Proper repair occurs in the majority of DNA damage. The only cure for sunburn is slow healing, although some skin creams can help with the symptoms.

Sunburn is caused by UV radiation, either from the sun or from artificial sources, such as welding arcs, the lamps used in sunbeds, and ultraviolet germicidal irradiation. It is a reaction of the body to the direct DNA damage, which can result from the excitation of DNA by UV-B light. This damage is mainly the formation of a thymine dimer. The damage is recognized by the body, which then triggers several defense mechanisms, including DNA repair to revert the damage and increased melanin production to prevent future damage. Melanin transforms UV-photons quickly into harmless amounts of heat without generating free radicals, and is therefore an excellent photoprotectant against direct and indirect DNA damage.

The pain may be caused by overproduction of a protein called CXCL5, which activates nerve fibres^[6].

Experiments with mice found that protection against sunburn by chemical sunscreens does not necessarily provide protection against other damaging effects of UV radiation such as enhanced melanoma growth.^[7]

Ultraviolet B (UVB) radiation causes dangerous sunburns and increases the risk of two types of skin cancer: basal-cell carcinomaand squamous cell carcinoma.^[1]^[2]

Some exposure to sunlight is not only harmless but positively necessary to health. Humans need vitamin D; most is synthesised in the body by exposure of the skin to sunlight, with some from the diet. People with darker skins need more sunlight to maintain vitamin D levels. The widespread concern about over-exposure to the sun causing cancer has led some people to go too far in avoiding exposure and using sunscreen; this can lead to vitamin D deficiency and the condition of rickets due to this deficiency, particularly in children, and particularly in climates with less sunshine. Cases of rickets are, indeed, on the increase. Twenty to thirty minutes of unimpeded exposure to the sun two to three times a week are recommended. ^[8]

[edit]Controversy over sunscreen

The statement sunburn causes skin cancer is considered accurate when it refers to either basal-cell carcinoma, the mildest form of cancer, or squamous cell carcinoma. However, this may be misleading when it comes to malignant melanoma (see picture: UVR sunburn melanoma)^{[citation needed]}. The statistical correlation between sunburn and melanoma is assumed to be due to a common cause — UV radiation. Instead, this correlation may be generated via different mechanisms. Direct DNA damage is ascribed by many medical doctors to a change in behaviour of the sunscreen user due to a false sense of security afforded by the sunscreen. While some researchers believe that these confounding factors can be controlled for effectively, ^[9] others believe there to be insufficient correction for light-skinned individuals and indirect DNA damage.^{[clarification needed]}

Topically applied sunscreen blocks UV rays as long as it does not penetrate into the skin. This prevents sunburn, suntanning, and skin cancer. If the sunscreen filter is absorbed into the skin, it prevents sunburn, but increases the amount of free radicals, which in turn increases the risk for malignant melanoma. The harmful effect of photo-excited sunscreen filters on living tissue has been shown in many photo-biological studies.^[10]^[11]^[12]^[13] Whether sunscreen prevents or promotes the development of melanoma depends on the relative importance of the protective effect from the topical sunscreen versus the harmful effects of the absorbed sunscreen.

The use of sunscreen is known to prevent the direct DNA damage that causes sunburn and the two most common forms of skin cancer, basal-cell carcinoma and squamous cell carcinoma.^[14] However, if sunscreen penetrates into the skin, it promotes indirect DNA damage, which causes the most lethal form of skin cancer, malignant melanoma.^[15] This form of skin cancer is rare, but it causes 75% of all skin cancer-related deaths. Increased risk of malignant melanoma in sunscreen users has been the subject of many epidemiological studies

Symptoms

Typically there is initial redness (erythema), followed by varying degrees of pain, proportional in severity to both the duration and intensity of exposure.

Other symptoms are edema, itching, peeling skin, rash, nausea, fever, and syncope. Also, a small amount of heat is given off from the burn, caused by the concentration of blood in the healing process, giving a warm feeling to the affected area. Sunburns may befirst- or second-degree burns.

One should immediately speak to a dermatologist if one develops a skin lesion that has an asymmetrical form, has darker edges than center, changes color, or becomes larger than 1/4 inch (6 mm). (see Melanoma)

Duration

Sunburn can occur in less than 15 minutes, and in seconds when exposed to non-shielded welding arcs or other sources of intense ultraviolet light. Nevertheless, the inflicted harm is often not immediately obvious.

After the exposure, skin may turn red in as little as 30 minutes but most often takes 2 to 6 hours. Pain is usually most extreme 6 to 48 hours after exposure. The burn continues to develop for 24 to 72 hours, occasionally followed by peeling skin in 3 to 8 days. Some peeling and itching may continue for several weeks.

Long-term low-intensity exposure to sunlight is known to cause significant ageing of the skin; other health effects are not accurately known. A particular example with very noticeable ageing is that of a 69-year-old truck driver in Chicago, USA who drove in the city for 28 years. A photograph of his face^[27]^[28] shows a great deal of ageing on the left side, where he was exposed to sunlight all day, while the right side has the "taut, unblemished face of an apparently much younger man".^[28]^[27] Window glass does not absorb UVA, which can penetrate the epidermis and upper layers of dermis. Chronic UVA exposure can cause photoageing: thickening of the epidermis and stratum corneum and destruction of elastic fibers; it can cause DNA mutations and toxicity which can lead to cancer, although less carcinogenic than UVB.

One of the most effective ways to prevent sunburn is to reduce the amount of UV radiation reaching the skin. The strength of sunlight is published in many locations as a UV index. The World Health Organization recommends to limit time in the midday sun (between 10 a.m. and 4 p.m.), to watch the UV index, to seek shade, to wear protective clothing and a wide-brim hat, and to use sunscreen.^[29]Sunlight is generally strongest when the sun is close to the highest point in the sky. Due to time zones and daylight saving time, this is not necessarily at 12 p.m., but often one to two hours later.

Commercial preparations are available that block UV light, known as sunscreens or sunblocks. They have a sunburn protection factor (SPF) rating, based on the sunblock's ability to suppress sunburn: The higher the SPF rating the lower the amount of direct DNA damage.

A sunscreen rated as SPF 10 blocks 90% of the sunburn-causing UVB radiation; an SPF20-rated sunscreen blocks 95%^{[citation needed]}. Modern sunscreens contain filters for UVA radiation as well as UVB. The stated protection factors are correct only if 2 μl of sunscreen is applied per square cm of exposed skin. This translates into about 28 ml (1 oz) to cover the whole body of an adult male, which is much more than many people use in practice. Although UVA radiation does not cause sunburn, it does contribute to skin aging and an increased risk of skin cancer. Many sunscreens provide broad-spectrum protection, meaning that they protect against both UVA and UVB radiation.

Research has shown that the best protection is achieved by application 15 to 30 minutes before exposure, followed by one reapplication 15 to 30 minutes after exposure begins. Further reapplication is necessary only after activities such as swimming, sweating, and rubbing.^[30] This varies based on the indications and protection shown on the label — from as little as 80 minutes in water to a few hours, depending on the product selected.

When one is exposed to any artificial source of occupational UV, special protective clothing (for example, welding helmets/shields) should be worn.

There is also evidence that common foods may have some protective ability against sunburn if taken for a period before the exposure.^[31] Beta-carotene and lycopene, chemicals found in tomatoes and other fruit, have been found to increase the skin's ability to resist the effects of UV light. In a 2007 study, after about 10–12 weeks of eating tomato-derived products, a decrease in sensitivity toward UV was observed in volunteers. Ketchup and tomato puree are both high in lycopene.^[32] Dark chocolate rich inflavonoids has also been found to have a similar effect if eaten for long periods before exposure.

Eyes

The eyes are also sensitive to sun exposure. Wrap-around sunglasses or the use by spectacle-wearers of glasses that block UV light reduce harmful UV radiation. UV light has been implicated in the development of age-related macular degeneration^[33], pterygium^[34] and cataract.^[35] Concentrated clusters of melanin, commonly known asfreckles, are often found within the iris.

[edit]Diet

Dietary factors influence susceptibility to sunburn, recovery from sunburn, and risk of secondary complications from sunburn. Several dietary antioxidants, including essential vitamins, have been shown to have some effectiveness for protecting against sunburn and skin damage associated with ultraviolet radiation, both in human and animal studies. Supplementation with Vitamin C and Vitamin E was shown in one study to reduce the amount of sunburn after a controlled amount of UV exposure.^[36] A review of scientific literature through 2007 found that beta carotene (Vitamin A) supplementation had a protective effect against sunburn, but that the effects were only evident in the long-term, with studies of supplementation for periods less than 10 weeks in duration failing to show any effects.^[37] Lutein, a carotenoid, was also found in a study on mice to protect against ultraviolet-induced inflammation and immunosuppression.^[38]

Sunburn increases the metabolic demands on the body, increasing the needs for water and other nutrients to prevent skin breakdown and secondary infections.^[39]

[edit]Treatment

The most important aspects of sunburn care are to avoid exposure to the sun while healing and to take precautions to prevent future burns. The best treatment for most sunburns is time. Most sunburns heal completely within a few weeks. Home treatments that help manage the discomfort or facilitate the healing process include using cool and wet cloths on the sunburned areas, taking frequent cold showers or baths, and applying soothing lotions that contain aloe vera^{[dubious – discuss]} to the sunburn areas. Topical steroids (such as 1% hydrocortisone cream) may also help with sunburn pain and swelling. The peeling that comes after some sunburn is inevitable. However, there are lotions that may relieve the itching. Acetaminophen (such as Tylenol), Nonsteroidal anti-inflammatory drugs (such as Ibuprofen or Naproxen), and Aspirin have all shown to reduce the pain of sunburns.^[40]

Sunburn

General Considerations

Most sunburns are first-degree (erythema) or superficial partial-thickness (blisters) burns. Skin changes from sunburn are maximal about 12–24 hours after exposure. Patients usually present to the emergency department for pain relief. Occasionally a patient with extensive superficial partial-thickness burns will require fluid resuscitation and parenteral analgesics for pain control.

Clinical Findings

Diagnosis is based on a history of exposure to the sun (or to ultraviolet light in tanning beds) and physical findings of erythema and blistering.

Treatment

Sunburn can be difficult to treat. Saline-soaked dressings or calamine lotion may provide some relief from pain and itching. Ibuprofen and other nonsteroidal anti-inflammatory agents work by blocking the production of prostaglandins that are thought to be important mediators of pain in sunburned skin. Oral and topical corticosteroids have not been shown to significantly improve symptoms or decrease healing time. Patients with extensive partial-thickness sunburn should receive treatment according to the guidelines described for other thermal burns.

Disposition

Almost all patients with sunburn may receive treatment on an outpatient basis. If there are large blisters, the patient should be seen again in 2–3 days to make sure that secondary infection has not developed. Patients should be advised to avoid prolonged ultraviolet light exposure to the sun in the future and to use a sunscreen (eg, over-the-counter preparations containing PABA [p-aminobenzoic acid] or dioxybenzone) before exposure. Patients requiring fluid resuscitation or parenteral analgesics should be hospitalized.

Electrical Burns

See Chapter 46.

Ocular Burns