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Chapter 33 Differential Diagnosis and Management of Fever in Trauma

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Chapter 33 Differential Diagnosis and Management of Fever in Trauma Differential Diagnosis and Management of Fever in Trauma Chapter 33 DIFFERENTIAL DIAGNOSIS AND MANAGEMENT OF FEVER IN TRAUMA CHRISTIAN POPA, MD* INTRODUCTION INFECTIOUS CONSIDERATIONS NONINFECTIOUS CAUSES OF FEVER Neurogenic Fever Drug Fever Pancreatitis Acalculous Cholecystitis Malignant Hyperthermia and Neuroleptic Malignant Syndrome Serotonin Syndrome Other Causes Atelectasis WORKUP OF FEVER EMPIRIC THERAPY TREATMENT OF FEVER SUMMARY * Colonel, Medical Corps, US Army; Critical Care Service, Department of Surgery, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, Maryland 20889 339 Combat Anesthesia: The First 24 Hours INTRODUCTION Fever is one of the most common physical abnor- dures. A recent prospective observational study of all malities in critically ill patients,1 and may be caused adult patients (n = 1,032) undergoing inpatient general by infectious or noninfectious etiologies. It is a specific surgical procedures during a 13-month period at an and well-coordinated reaction to a challenge or insult academic military medical center found an incidence and is part of the systemic inflammatory response. of early postoperative fever (defined as temp >100.4˚F Macrophages and polymorphonuclear leukocytes in the 72 hours following surgery) of 23.7%.7 release endogenous pyrogens such as interleukin-1 Multiple studies of critically ill patients have fairly that orchestrate a variety of biochemical and physi- consistently attributed infectious causes to fever in ological responses, of which temperature elevation approximately one-half of cases,8–10 with pneumonia, is only one. Interleukin-1 (and probably other cyto- sinusitis, urinary tract, bloodstream, wound and kines) stimulates the production of prostaglandins in skin/soft tissue, and intraabdominal infections being the fever-mediating region of the preoptic area of the frequent etiologies.11–13 Noninfectious etiologies are anterior hypothalamus, resulting in fever.2 responsible for the remaining febrile episodes. These Patients with traumatic injuries have an increased noninfectious causes of fever may include myocardial incidence of both fever and infectious complications, infarction, cerebrovascular hemorrhage, thrombophle- resulting in frequent diagnostic workups. A study of bitis, drug reactions, transfusion reactions, malignant 510 critically ill trauma patients found that 79% of pa- hyperthermia, heat stroke, pancreatitis, and acute ad- tients staying in a surgical and trauma intensive care renal insufficiency.1,14–18 Because trauma patients are at units (ICUs) for at least 7 days were febrile, and 80% increased risk for thromboembolic disease, fever in the had leukocytosis at some point during their first week presence of a new or worsening oxygen requirement of ICU care.3 A larger retrospective review of 37,448 and/or persistent tachycardia should also prompt trauma/neurologic ICU admissions found an overall consideration of pulmonary embolism as a possible fever incidence density of 38.2 per 100 days, which was cause. A review of 311 patients with angiography- higher than in other surgical, medical, or postcardiac proven pulmonary embolism found a 14% incidence surgery patients.4 Although the presence of fever al- of otherwise unexplained fever (usually low grade).19 ways prompts concern about infection, it is recognized It is important to note that not all patients with infec- that many trauma patients will become febrile despite tions are febrile. For unclear reasons, approximately persistently negative cultures. In these patients, it is 35% of septic patients are normothermic at presenta- thought that the severity of injury frequently leads tion and another 10% are hypothermic.20 Septic patients to increased tissue necrosis, and that the associated who fail to develop a temperature have a significantly stress response causes an increase in granulocytes in higher mortality than febrile septic patients. Therefore, the peripheral blood. The increased tissue necrosis and patients at risk for infection who manifest unexplained increase in granulocytes lead to subsequent increase hypothermia should be aggressively evaluated. in temperature due to the inflammation itself and not In summary, although fever often has a noninfec- necessarily due to an underlying infection.5 tious etiology, the provider must remain vigilant and Surgery, which many trauma patients will undergo, appropriately evaluate fever when it represents a new elicits a similar inflammatory response, and both in- finding or a change in the patient’s condition. He or flammation and macrophage phagocytosis of extrava- she must also employ appropriate empiric or directed sated blood, common benign postoperative events, antimicrobial therapy along with such proven mea- have been implicated in a febrile response shortly after sures as wound irrigation, removal of infected foreign surgery.6 As a result, postoperative fever is a relatively bodies, debridement of devitalized tissue, and drain- common event immediately after major surgical proce- age of abscesses. INFECTIOUS CONSIDERATIONS In trauma patients who survive longer than 3 days, injuries because high-velocity projectiles and blast infection is second only to severe head injury as the devices employed as weapons cause a more severe cause of death, and an estimated 37% to 45% of all injury than commonly seen in civilian settings, and the trauma patients will experience an infectious complica- accompanying wounds are frequently contaminated tion such as pneumonia during their initial hospital- by clothing, soil, and environmental debris.22 Because ization.21 Furthermore, there is generalized agreement of these factors and delay before definitive surgery, war that war wounds are distinct from civilian traumatic wounds have a higher infection potential compared 340 Differential Diagnosis and Management of Fever in Trauma to civilian injuries, with an incidence of 3.9% in the 2006 show that of the 26 patients (40%) who received a first 2 weeks after injury reported in one Vietnam-era course of antibiotics, 13 were treated for Acinetobacter, study.23 In addition, military trauma patients often 9 for Klebsiella species, 6 for Pseudomonas aeruginosa, 5 have multiple injuries at multiple sites, allowing mul- for Enterobacter species, and 6 for methicillin-resistant tiple avenues for possible infections to occur, so it is S aureus.27 This and other data suggest that the pat- not at all infrequent for these patients to be infected at tern of causative organisms is similar in the Iraq and different sites with different organisms simultaneously. Afghanistan theaters. Furthermore, the subsequent insertion of various In patients with negative cultures and without tubes and drains allows easy access of organisms in evidence of war injury-related infection, rare but the intensive care environment into normally sterile notable febrile infections that have been reported sites of these already critically ill patients.24 in soldiers returning from Iraq and Afghanistan A 2003–2004 survey by Yun et al of infections en- include tuberculosis, malaria, Q fever, brucellosis, countered in combat support hospitals in Iraq25 found and leishmaniasis. Tuberculosis is endemic in central that gram-positive bacteria were responsible for and southwest Asia; the World Health Organization most clinical infections in US troops with coagulase- estimates a prevalence of 149 cases per 100,000 per- negative staphylococci, accounting for 34% of isolates, sons in Afghanistan and 45 cases per 100,000 persons Staphylococcus aureus for 26%, and streptococcal spe- in Iraq in2011.28 The overall deployment-associated cies for 11%. In contrast, the 732 cultures obtained conversion rate has been estimated at 2.5%.29 In Iraq, from the predominantly Iraqi population yielded chloroquine-susceptible Plasmodium vivax malaria mostly gram-negative bacteria: Klebsiella pneumoniae occurs at low rates (150 cases per year in 2008) and (13%), Acinetobacter calcoaceticus-baumannii complex there have been no reported cases among US military (11%), and Pseudomonas aeruginosa (10%). Both gram- forces serving there. Conversely, there were 467,123 negative and gram-positive bacteria were resistant malaria cases in Afghanistan, as reported to the to a broad array of antimicrobial agents. A similar WHO in 2008.30 Transmission is seasonal from June retrospective review by Petersen et al of the infection to November, with negligible transmission occurring patterns of 211 casualties (of which 85% were Iraqi between December and April. Most cases involve P nationals) evacuated to the USNS Comfort from the vivax, but P falciparum is also transmitted.29 Although Iraqi theater during Operation Iraqi Freedom26 found soldiers are routinely issued malaria prophylaxis, that 26.5% met criteria for infection. Patients with noncompliance remains a significant issue. An in- blast injuries, soft tissue injuries, more than three vestigation of an outbreak of P vivax among Army wound sites, loss of limb, abdominal trauma, and a Rangers after deployment to eastern Afghanistan higher Injury Severity Score (ISS) were more likely to yielded a self-reported 52% rate of adherence to be infected. Most infections involved wounds, which mefloquine prophylaxis.31 accounted for 84% of cases, followed by bloodstream Q fever is a zoonotic infection caused by Coxiella infections (38%) and positive sputum cultures (21%). burnetii usually acquired through inhalation of infected Acinetobacter infections were most common,
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