The Febrile Alcoholic in the Emergency Department KEITH D. WRENN, MD, STEVE LARSON, MD
The authors retrospectively reviewed the charts of 31 alcoholic patients admitted with fever without a defined source. In our population 58% of patients were subsequently found to have an infectious cause for their fever. Pneumonia was the most common infection, but occult urinary tract infections were seen surprisingly often. Noninfectious but serious disorders, such as delirium tremens, prolonged postlctal state, and subarachnoid hemorrhage, were also common. Infectious and noninfectious causes commonly coexisted. The most common noninfectious cause was alcohol withdrawal, with or without seizures. The authors believe that indigent, malnourished, chronic alcoholics with fever for which a source cannot be readily identified, should usually be admitted to the hospital for observation and to await culture results. (Am J Emerg Med 1991;9:5760. Copyright 0 1991 by W.9. Saunders Company)
When a chronic alcohol abuser presents with fever, a diagnostic and therapeutic dilemma results. The clinician is faced with a vast array of possible causes as well as an often uncooperative, unreliable patient. In our emergency department (ED), which serves a large population of chronic malnourished alcoholics, we are commonly presented with this problem. It has been our practice to admit such patients to the hospital regardless of physical findings, laboratory results, or radiograph findings. We decided to look at our population of febrile alcoholics in an attempt to determine what parameters might help predict morbidity. We also hoped to gain some insight into the natural history of the febrile alcoholic. METHODS All patients who were admitted with the diagnosis “Alcoholic with fever” over 4 months were eligible for our retrospective review. Two summer months and two winter months were randomly selected over a 2-year period. Fever was defined as an oral temperature greater than or equal to 378°C (100°F). Alcoholic patients admitted with fever due to a specific diagnosis such as pneumonia, tuberculosis, delirium tremens, or meningitis were excluded. Fourteen patients whose records were unavailable for review were also ex-
From the Department of Medicine and the Emergency Medicine Residency, Grady Memorial Hospital, Emory University School of Medicine, Atlanta, GA. Manuscript received March 16, 1990; revision accepted July 30, 1990. Address reprint requests to Dr. Wrenn: Emergency Department, Box 655, Strong Memorial Hospital, 601 Elmwood Ave, Rochester, NY 14642. Key Words: Alcoholism, complications, fever. Copyright 0 1991 by W.B. Saunders Company 0735-6757/91/0901-0017$5.00/O
eluded. The final population reviewed represented alcoholics found to have a fever in the ED but in whom there was no definite source for the fever after initial ED evaluation. All patients were chronic alcoholics who, by self-report, drank at least two pints of 80-proof alcohol each day. Records were reviewed retrospectively, and data collected included the chief complaints, pertinent positive and negative physical findings, age, sex, appropriate laboratory and culture results, radiology reports and discharge diagnoses. All patients were evaluated by medicine or emergency medicine residents and had a chest roentgenogram and urinalysis performed in the ED. Statistical comparison of the temperatures of the infected versus the noninfected patients was done using a standard t-test of the means, assuming equal variances. In the case of the white blood cell counts a t-test of the means assuming unequal variances was used. RESULTS The characteristics of the 31 patients are presented in Table 1. The presenting problems are listed in Table 2. Several patients had more than one complaint. There was a preponderance of patients with either seizures (lo), gastrointestinal complaints (9), or cough (5). The mean admission temperature for the group as a whole was 383°C (100.9”F), with a range of 37.7”C to 39.5”C. There were three patients whose ED temperature was not recorded, who nevertheless were admitted with the diagnosis “fever.” These patients all had temperatures above 37.8”C later in the course of their ED stay. In one patient the presenting temperature was 37.7”C, but hours later he mounted a temperature greater than 37.8”C, which prompted admission to the hospital. Of the 31 patients, 18 had either a definite or possible infectious etiology. These definite or possible infectious etiologies are listed in Table 3, which encompasses all the discharge diagnoses; once again, several patients had multiple diagnoses. Ten patients were felt to have totally noninfectious causes for the fever, and these are also listed in Table 3. Eighteen patients were felt to potentially have both infectious and noninfectious causes of fever, but for the sake of simplicity are listed under the infectious category. Among those ultimately diagnosed with infections, the mean temperature was slightly higher (38.8”C) than among those without infection (38.3”C) but no statistical difference was noted (P = .09). The range of temperatures among the infected patients was 38.2”C to 39.5”C. The range of temperatures for the noninfected patients was 37.7” to 39°C (Figure 1). Admission white blood cell (WBC) counts were available
57
AMERICAN
58
TABLE 1.
JOURNAL
Patient Characteristics
Age
Mean
Sex
Male Female
TABLE 3. 46 (Range 30-76) 26 5
in 27 patients and ranged from 3,900/mm3 to 29,000/mm3with a mean of 10,600/mm3. When separated according to those with infection (16 patients) and those without (1 l), the mean WBC was 11,100/mm3 and 9,900/mm3 respectively. There was no statistical difference (P = S9). The range was much wider in the infected group (3,900/mm3 to 29,000/mm3) than in the noninfected group (4,000/mm3 to 16,000/mm3) (Figure 2). The most frequently documented infection was pneumonia, which occurred in six patients. Three of these patients had Hemophilus influenza cultured from either sputum or blood; two were culture negative, and one had streptococcal septicemia. The only death in this series occurred in the latter patient. One additional patient was eventually found to have a lung abscess. Six of the 7 patients with documented parenchymal lung infections were known to have a history of seizures, either remotely or recently. Urinary tract infections (UTIs) were found in four patients. In this series, three patients had Klebsiella species cultured from the urine, and in one patient, Escherichia coli. There were three patients with soft tissue infections: one patient had a cellulitis and staphylococcus epidermidis was cultured from his blood; one had an abscess in his lower leg from which Acinetobacter was cultured; and one had a perirectal abscess. Both of the latter patients required surgical drainage procedures. The other infections occurred singly and can be seen in Table 3. Viral diseases were proven or suspected in four patients. The most common noninfectious etiologies postulated to cause fever (Table 3) were alcohol withdrawal (14) and alcoholic hepatitis (13). Seizure activity by itself, without alcohol withdrawal, was suspected in two patients. Rhabdomyolysis and pancreatitis were incriminated in two patients each. TABLE 2.
Presenting Problems N (%)
Seizure Abdominal Diarrhea
pain, Nausea, Vomiting
Cough Headache Hallucinations Dysuria “Hurting all over” Cramping hands and legs Altered mental status Lethargy Weakness Joint Pain Hematemesis Pleuritic chest pain Unilateral leg edema
OF EMERGENCY
10 (32) 5 (16) 4 (13)
5 (16) 2 (7) 2 (7) 2 (7) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3)
MEDICINE
l Volume 9, Number
1 a January 1991
Discharge Diagnoses
Infectious Definite Pneumonia Lung abscess Urinary tract infection Cellulitis Leg abscess Perirectal abscess Gonococcal urethritis Salmonellosis Hepatitis S Possible Viral gastroenteritis Viral syndrome Upper respiratory infection
N (%)
Noninfectious
6 (1%
Alcohol withdrawal Alcoholic hepatitis Alcoholic ketoacidosis Rhabdomyolysis Seizure disorder Pancreatitis Gout Subarachnoid hemorrhage Wernicke’s encephalopathy
1 (3) 4 (13) 1 (3) f (3) 1 (3) 1 (3) 1 (3) f (3)
N (%)
14 13 3 2 2 2 1
(45) (42) (10) (7) (7) (7) (3) 1 (3) t (3)
1 (3) 1 (3) 1 (3)
DISCUSSION More often than not, in our experience (18 of 31 patients, 58%), febrile alcoholics turn out to have an infection. Even if all 14 patients whose charts we could not review had had noninfectious causes of fever, there would still be a considerable proportion (40%) with infectious causes. Furthermore, the noninfectious causes of fever were often sufficient to warrant admission. One patient suffered a subarachnoid hemorrhage; one had a polyarticular attack of gout that prevented ambulation; one had a prolonged postictal state with a transient left hemiparesis; one had hematemesis, and two eventually developed full-blown delirium tremens. No easy-to-obtain data reliably distinguished the infected from the noninfected patients. Figure 1 shows the considerable overlap in temperatures between infected and noninfected patients. While the temperatures of the infected patients tended to be higher, no practical cut-off value can be ascertained. Although 100% sensitivity is desirable in using the temperature to make decisions about admitting febrile alcoholics, even when accepting a sensitivity of 90% to 95% (see the dashed line in Figure l), not only is the relatively mild fever of 38.4% (101.2”F) the cut-off value in our series, but the specificity is only 50%. Thus we feel that the degree of elevation in temperature is an inadequate discriminator between infectious and noninfectious causes. Extremes of temperature (above 39.o”C) were more likely to be due to infectious causes, but alcohol withdrawal alone has been noted to cause fever as high as 41.4”C, and temperatures as high as 39.4”C have been noted with Laennec’s cirrhosis.“’ The situation with the WBC is analogous to that with fever (Figure 2). No practical cut-off value can be seen as only extremes of elevation (greater than 16,000/mm3) occur more often with infection. The alcoholic’s predisposition to leukopenia may contribute to this overlap.3 The fact that almost one-fourth of our patients had an infection in the lungs is not surprising. In two previous studies dealing particularly with the withdrawal syndrome, infectious lung diseases were seen in between 25%’ and 5O%4 of patients. Alcoholics are unusually predisposed to pneumonia, in part because of impaired local defense factors.4.5 but more importantly because of their tendency to aspirate4 Not only do they find themselves in situations predisposing to aspiration (vomiting, seizures, altered mental states), but
WRENN AND LARSON I FEBRILE ALCOHOLIC
39.4 -
59
.
: . . . : ii . . . . . . ;;i 38.6 . ‘___“‘__‘T’_,__“‘____“--__~~~ t . f 38.2 39.0 -
.
.
. . . _________. . l
: 37.8 -
.
.
37.4. I
37.01 Infected (mean 38.8) (range 38.2-39.5)
Noninfected (mean 38.3) (range 37.7-39.0)
FIGURE 1. Temperature in febrile alcoholics.
also intoxication leads to the loss of glottic reflexes.6 This tendency to aspirate is evident in the fact that six of the seven patients in this series with a lung infection had a known seizure disorder. The one death in our series occurred in a patient with pneumonia. In this case, the initial roentgenogram was unremarkable and clinical pneumonia with roentgenographic changes was discovered 3 days into the hospitalization. Rose et al made the point that in 79% of the alcoholics in their series with pneumonia, the process developed in the hospital, usually between the third and tenth days.4 Five of six patients (83%) in our series who had pneumonia on admission did not have physical signs of lobar consolidation. Two of these patients had bilateral crackles or bilateral rhonchi or wheezes recorded. The lack of associated diagnostic physical findings in the setting of pneumonia has previously been noted.4 On the other hand, in one patient admitted after a seizure, signs of consolidation in the left lower lung field were noted, but the chest roentgenogram was remarkable only for a bleb in the right upper lobe. This patient’s fever resolved after receiving penicillin for 48 hours. In two patients, the initial chest roentgenogram was interpreted as unremarkable, but pneumonia was eventually diagnosed. In one patient who had suffered a seizure, the roentgenogram was done by portable technique and a retrocardiac left lower lobe infiltrate was missed. In another patient, an abdominal computed tomography scan incidentally revealed a left lower lobe pulmonary infiltrate, not visible on the chest roentgenogram. A discrepancy between the clinical course of the patient and roentgenographic findings is not uncommon.4 Interestingly, none of the patients with UT1 complained specifically of symptoms referable to the urinary tract. Two of the four patients were men, one of whom had documented prostatic enlargement and a postvoid residual on intravenous pyelography, while the other had a known neurogenic bladder. Two of the patients with a UT1 complained of generalized cramping or myalgias: one was admitted after seizures and one had a chief complaint of a cough and was found to
have a concomitant pneumonia. This paucity of symptoms might reflect the possibility that these patients’ UTIs were not the primary cause of their fevers, or alternatively might reflect that the history in alcoholic patients is often unreliable. In contrast, neither of the patients who complained of dysuria on admission turned out to have a UTI. The frequency of the clinical diagnosis of alcoholic hepatitis in this series is not surprising, given the severity of the drinking problem in these patients. With the exception of one case, however, all our patients had only moderately elevated liver enzymes, with the aspartate aminotransferase level on the order of twice normal. Because the clinical diagnosis does not necessarily correlate with histologic tindings and because fever in Laennec’s cirrhosis seems to occur in patients with severe clinical signs (jaundice, hepatomegaly, and fluid retention)‘,’ the tendency to attribute fever to abnormal liver enzymes is probably, more often that not, a mistake. Seizures and alcohol withdrawal have both been shown to cause fever in the absence of other identifiable causes.8-1o It has also been shown that, in both situations, concomitant infections, particularly pneumonias, are common.‘*4 A total of 14 patients were thought to be in some stage of alcohol withdrawal. Withdrawal, with or without seizures, was commonly accompanied by multiple other potential causes of fever as has been reported by others.’ The other causes included pneumonia (6), urinary tract infection (I), a leg abscess (l), pancreatitis (2), rhabdomyolysis (2), alcoholic liver disease (l), an upper respiratory tract infection (l), and a suspected viral syndrome (1). Volume depletion has been implicated as a cause of fever in alcohol withdrawal and the fever often resolves after volume repletion alone.4 Only 4 of the 14 patients with the alcohol withdrawal syndrome had no other significant cause of fever noted. Of interest is the fact that no cases of occult central nervous system infections were discovered despite the fact that fever and altered mental status coexisted in six patients in the absence of another identifiable cause of fever. In all six cases, the lumbar puncture showed sterile cerebrospinal fluid (CSF). In one case, bloody CSF was the clue to a subarachnoid hemorrhage. In another patient with seizures,
26k -
22k ”
18k-
s
14klOk6k -
Infected (mean 11.1) (range 3.9k-29k)
Noninfected (mean 9.9) (range 4.0k- 16.5k)
FIGURE 2. WBC in febrile alcoholics.
60
AMERICAN
JOURNAL
a mildly elevated protein (71 mg/dL) was seen with a traumatic tap (600 red blood cells [RBCs] and no WBCs in tube 1 and 20 RBCs and no WBCs in tube 4). Despite these negative findings, we agree with the statement “confusion or obtundation in alcoholic patients . . . should never be attributed to toxicity associated with infection, alcoholism, or hepatic decompensation, until meningitis has been ruled out by lumbar puncture. ” The initial history and physical examination in the alcoholic may be particularly unreliable in guiding the clinician to the correct diagnosis. In several cases symptoms pointed to one organ system while the infection was found in a different organ system. Alcoholics may also harbor more than one focus of infection. One patient had four concomitant infections (pneumonia, trichomonas vaginitis, perirectal abscess, and UTI). CONCLUSIONS The alcoholic is predisposed to fever from a vast array of causes. In summary, the following points can be made. Alcoholics present with multiple problems, many of which can cause fever. Both infectious and noninfectious causes may coexist and multiple infections may coexist. Commonly used clinical parameters like the WBC and degree of temperature elevation are not practical ways to differentiate infectious from noninfectious causes. Noninfectious causes were often, in and of themselves, sufftcient to warrant admission in this series. The initial history was often incomplete and misleading. The most common infection in this study was pneumonia with characteristic or diagnostic clinical features developing after admission. Pneumonia also commonly developed in a setting known to predispose to alteration in mental status
OF EMERGENCY
MEDICINE
W Volume
9, Number
1 n January
1991
(for example seizures). There was often poor correlation between physical findings and roentgenogram. UTIs were not as rare in this series as in others and were often unsuspected. The most common noninfectious cause of fever was alcohol withdrawal with or without seizures. Clinically diagnosed alcoholic hepatitis probably only occasionally causes fever. There is a necessity to maintain a high index of suspicion and a low threshold for diagnostic testing and treatment; repeat examinations need to be performed and observation in the hospital is often necessary. REFERENCES 1. Tavel ME, Davison W, Batterton TD: A critical analysis of mortality associated with delerium tremens-Review of 39 fatalities in a nine-year period. Am J Med Sci 1961;242:18-29 2. Tisdale WA, Klatskin G: The fever of Laennec’s cirrhosis. Yale J Biol Med 1960;33:94-106 3. McFarland W, Libre EP: Abnormal leukocyte response in alcoholism. Ann Intern Med 1963;59:865-877 4. Rose HD, Golbert TM, Sanz CZ, Leitschuh TH. Fever during acute alcohol withdrawal. Am J Med Sci 1970;260:112-121 5. Shulman JA, Phillips LA, Petersdorf RG: Errors and hazards in the diagnosis and treatment of bacterial pneumonias. Ann Intern Med 1965;62:41-58 6. Nungester WJ, Klepser RG: A possible mechanism of lowered resistance to pneumonia. J Infect Dis 1938;63:94-102 7. Sherlock S: Alcoholic liver disease: Clinical patterns and diagnosis. Acta Med Stand 1985;703:103-110 (suppl) 8. Wachtel TJ, Steele GH, Day JA: Natural history of fever following seizure. Arch Intern Med 1987;147:1153-1155 9. lsbell H. Fraser HG. Wikler A. et al: An experimental study of the etiology of “rum fits” and delirium tremens. Quart J Stud Alcohol 1955;16:1-33 10. Thompson WL, Johnson AD, Maddrey WL, et al: Diazepam and paraldehyde for treatment of severe delirium tremens. Ann Intern Med 1975;82:175-180 11. Carpenter RR, Petersdorf RG. The clinical spectrum of bacterial meningitis. Am J Med 1962;33:262-275
The authors retrospectively reviewed the charts of 31 alcoholic patients admitted with fever without a defined source. In our population 58% of patients were subsequently found to have an infectious cause for their fever. Pneumonia was the most common infection, but occult urinary tract infections were seen surprisingly often. Noninfectious but serious disorders, such as delirium tremens, prolonged postlctal state, and subarachnoid hemorrhage, were also common. Infectious and noninfectious causes commonly coexisted. The most common noninfectious cause was alcohol withdrawal, with or without seizures. The authors believe that indigent, malnourished, chronic alcoholics with fever for which a source cannot be readily identified, should usually be admitted to the hospital for observation and to await culture results. (Am J Emerg Med 1991;9:5760. Copyright 0 1991 by W.9. Saunders Company)
When a chronic alcohol abuser presents with fever, a diagnostic and therapeutic dilemma results. The clinician is faced with a vast array of possible causes as well as an often uncooperative, unreliable patient. In our emergency department (ED), which serves a large population of chronic malnourished alcoholics, we are commonly presented with this problem. It has been our practice to admit such patients to the hospital regardless of physical findings, laboratory results, or radiograph findings. We decided to look at our population of febrile alcoholics in an attempt to determine what parameters might help predict morbidity. We also hoped to gain some insight into the natural history of the febrile alcoholic. METHODS All patients who were admitted with the diagnosis “Alcoholic with fever” over 4 months were eligible for our retrospective review. Two summer months and two winter months were randomly selected over a 2-year period. Fever was defined as an oral temperature greater than or equal to 378°C (100°F). Alcoholic patients admitted with fever due to a specific diagnosis such as pneumonia, tuberculosis, delirium tremens, or meningitis were excluded. Fourteen patients whose records were unavailable for review were also ex-
From the Department of Medicine and the Emergency Medicine Residency, Grady Memorial Hospital, Emory University School of Medicine, Atlanta, GA. Manuscript received March 16, 1990; revision accepted July 30, 1990. Address reprint requests to Dr. Wrenn: Emergency Department, Box 655, Strong Memorial Hospital, 601 Elmwood Ave, Rochester, NY 14642. Key Words: Alcoholism, complications, fever. Copyright 0 1991 by W.B. Saunders Company 0735-6757/91/0901-0017$5.00/O
eluded. The final population reviewed represented alcoholics found to have a fever in the ED but in whom there was no definite source for the fever after initial ED evaluation. All patients were chronic alcoholics who, by self-report, drank at least two pints of 80-proof alcohol each day. Records were reviewed retrospectively, and data collected included the chief complaints, pertinent positive and negative physical findings, age, sex, appropriate laboratory and culture results, radiology reports and discharge diagnoses. All patients were evaluated by medicine or emergency medicine residents and had a chest roentgenogram and urinalysis performed in the ED. Statistical comparison of the temperatures of the infected versus the noninfected patients was done using a standard t-test of the means, assuming equal variances. In the case of the white blood cell counts a t-test of the means assuming unequal variances was used. RESULTS The characteristics of the 31 patients are presented in Table 1. The presenting problems are listed in Table 2. Several patients had more than one complaint. There was a preponderance of patients with either seizures (lo), gastrointestinal complaints (9), or cough (5). The mean admission temperature for the group as a whole was 383°C (100.9”F), with a range of 37.7”C to 39.5”C. There were three patients whose ED temperature was not recorded, who nevertheless were admitted with the diagnosis “fever.” These patients all had temperatures above 37.8”C later in the course of their ED stay. In one patient the presenting temperature was 37.7”C, but hours later he mounted a temperature greater than 37.8”C, which prompted admission to the hospital. Of the 31 patients, 18 had either a definite or possible infectious etiology. These definite or possible infectious etiologies are listed in Table 3, which encompasses all the discharge diagnoses; once again, several patients had multiple diagnoses. Ten patients were felt to have totally noninfectious causes for the fever, and these are also listed in Table 3. Eighteen patients were felt to potentially have both infectious and noninfectious causes of fever, but for the sake of simplicity are listed under the infectious category. Among those ultimately diagnosed with infections, the mean temperature was slightly higher (38.8”C) than among those without infection (38.3”C) but no statistical difference was noted (P = .09). The range of temperatures among the infected patients was 38.2”C to 39.5”C. The range of temperatures for the noninfected patients was 37.7” to 39°C (Figure 1). Admission white blood cell (WBC) counts were available
57
AMERICAN
58
TABLE 1.
JOURNAL
Patient Characteristics
Age
Mean
Sex
Male Female
TABLE 3. 46 (Range 30-76) 26 5
in 27 patients and ranged from 3,900/mm3 to 29,000/mm3with a mean of 10,600/mm3. When separated according to those with infection (16 patients) and those without (1 l), the mean WBC was 11,100/mm3 and 9,900/mm3 respectively. There was no statistical difference (P = S9). The range was much wider in the infected group (3,900/mm3 to 29,000/mm3) than in the noninfected group (4,000/mm3 to 16,000/mm3) (Figure 2). The most frequently documented infection was pneumonia, which occurred in six patients. Three of these patients had Hemophilus influenza cultured from either sputum or blood; two were culture negative, and one had streptococcal septicemia. The only death in this series occurred in the latter patient. One additional patient was eventually found to have a lung abscess. Six of the 7 patients with documented parenchymal lung infections were known to have a history of seizures, either remotely or recently. Urinary tract infections (UTIs) were found in four patients. In this series, three patients had Klebsiella species cultured from the urine, and in one patient, Escherichia coli. There were three patients with soft tissue infections: one patient had a cellulitis and staphylococcus epidermidis was cultured from his blood; one had an abscess in his lower leg from which Acinetobacter was cultured; and one had a perirectal abscess. Both of the latter patients required surgical drainage procedures. The other infections occurred singly and can be seen in Table 3. Viral diseases were proven or suspected in four patients. The most common noninfectious etiologies postulated to cause fever (Table 3) were alcohol withdrawal (14) and alcoholic hepatitis (13). Seizure activity by itself, without alcohol withdrawal, was suspected in two patients. Rhabdomyolysis and pancreatitis were incriminated in two patients each. TABLE 2.
Presenting Problems N (%)
Seizure Abdominal Diarrhea
pain, Nausea, Vomiting
Cough Headache Hallucinations Dysuria “Hurting all over” Cramping hands and legs Altered mental status Lethargy Weakness Joint Pain Hematemesis Pleuritic chest pain Unilateral leg edema
OF EMERGENCY
10 (32) 5 (16) 4 (13)
5 (16) 2 (7) 2 (7) 2 (7) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3)
MEDICINE
l Volume 9, Number
1 a January 1991
Discharge Diagnoses
Infectious Definite Pneumonia Lung abscess Urinary tract infection Cellulitis Leg abscess Perirectal abscess Gonococcal urethritis Salmonellosis Hepatitis S Possible Viral gastroenteritis Viral syndrome Upper respiratory infection
N (%)
Noninfectious
6 (1%
Alcohol withdrawal Alcoholic hepatitis Alcoholic ketoacidosis Rhabdomyolysis Seizure disorder Pancreatitis Gout Subarachnoid hemorrhage Wernicke’s encephalopathy
1 (3) 4 (13) 1 (3) f (3) 1 (3) 1 (3) 1 (3) f (3)
N (%)
14 13 3 2 2 2 1
(45) (42) (10) (7) (7) (7) (3) 1 (3) t (3)
1 (3) 1 (3) 1 (3)
DISCUSSION More often than not, in our experience (18 of 31 patients, 58%), febrile alcoholics turn out to have an infection. Even if all 14 patients whose charts we could not review had had noninfectious causes of fever, there would still be a considerable proportion (40%) with infectious causes. Furthermore, the noninfectious causes of fever were often sufficient to warrant admission. One patient suffered a subarachnoid hemorrhage; one had a polyarticular attack of gout that prevented ambulation; one had a prolonged postictal state with a transient left hemiparesis; one had hematemesis, and two eventually developed full-blown delirium tremens. No easy-to-obtain data reliably distinguished the infected from the noninfected patients. Figure 1 shows the considerable overlap in temperatures between infected and noninfected patients. While the temperatures of the infected patients tended to be higher, no practical cut-off value can be ascertained. Although 100% sensitivity is desirable in using the temperature to make decisions about admitting febrile alcoholics, even when accepting a sensitivity of 90% to 95% (see the dashed line in Figure l), not only is the relatively mild fever of 38.4% (101.2”F) the cut-off value in our series, but the specificity is only 50%. Thus we feel that the degree of elevation in temperature is an inadequate discriminator between infectious and noninfectious causes. Extremes of temperature (above 39.o”C) were more likely to be due to infectious causes, but alcohol withdrawal alone has been noted to cause fever as high as 41.4”C, and temperatures as high as 39.4”C have been noted with Laennec’s cirrhosis.“’ The situation with the WBC is analogous to that with fever (Figure 2). No practical cut-off value can be seen as only extremes of elevation (greater than 16,000/mm3) occur more often with infection. The alcoholic’s predisposition to leukopenia may contribute to this overlap.3 The fact that almost one-fourth of our patients had an infection in the lungs is not surprising. In two previous studies dealing particularly with the withdrawal syndrome, infectious lung diseases were seen in between 25%’ and 5O%4 of patients. Alcoholics are unusually predisposed to pneumonia, in part because of impaired local defense factors.4.5 but more importantly because of their tendency to aspirate4 Not only do they find themselves in situations predisposing to aspiration (vomiting, seizures, altered mental states), but
WRENN AND LARSON I FEBRILE ALCOHOLIC
39.4 -
59
.
: . . . : ii . . . . . . ;;i 38.6 . ‘___“‘__‘T’_,__“‘____“--__~~~ t . f 38.2 39.0 -
.
.
. . . _________. . l
: 37.8 -
.
.
37.4. I
37.01 Infected (mean 38.8) (range 38.2-39.5)
Noninfected (mean 38.3) (range 37.7-39.0)
FIGURE 1. Temperature in febrile alcoholics.
also intoxication leads to the loss of glottic reflexes.6 This tendency to aspirate is evident in the fact that six of the seven patients in this series with a lung infection had a known seizure disorder. The one death in our series occurred in a patient with pneumonia. In this case, the initial roentgenogram was unremarkable and clinical pneumonia with roentgenographic changes was discovered 3 days into the hospitalization. Rose et al made the point that in 79% of the alcoholics in their series with pneumonia, the process developed in the hospital, usually between the third and tenth days.4 Five of six patients (83%) in our series who had pneumonia on admission did not have physical signs of lobar consolidation. Two of these patients had bilateral crackles or bilateral rhonchi or wheezes recorded. The lack of associated diagnostic physical findings in the setting of pneumonia has previously been noted.4 On the other hand, in one patient admitted after a seizure, signs of consolidation in the left lower lung field were noted, but the chest roentgenogram was remarkable only for a bleb in the right upper lobe. This patient’s fever resolved after receiving penicillin for 48 hours. In two patients, the initial chest roentgenogram was interpreted as unremarkable, but pneumonia was eventually diagnosed. In one patient who had suffered a seizure, the roentgenogram was done by portable technique and a retrocardiac left lower lobe infiltrate was missed. In another patient, an abdominal computed tomography scan incidentally revealed a left lower lobe pulmonary infiltrate, not visible on the chest roentgenogram. A discrepancy between the clinical course of the patient and roentgenographic findings is not uncommon.4 Interestingly, none of the patients with UT1 complained specifically of symptoms referable to the urinary tract. Two of the four patients were men, one of whom had documented prostatic enlargement and a postvoid residual on intravenous pyelography, while the other had a known neurogenic bladder. Two of the patients with a UT1 complained of generalized cramping or myalgias: one was admitted after seizures and one had a chief complaint of a cough and was found to
have a concomitant pneumonia. This paucity of symptoms might reflect the possibility that these patients’ UTIs were not the primary cause of their fevers, or alternatively might reflect that the history in alcoholic patients is often unreliable. In contrast, neither of the patients who complained of dysuria on admission turned out to have a UTI. The frequency of the clinical diagnosis of alcoholic hepatitis in this series is not surprising, given the severity of the drinking problem in these patients. With the exception of one case, however, all our patients had only moderately elevated liver enzymes, with the aspartate aminotransferase level on the order of twice normal. Because the clinical diagnosis does not necessarily correlate with histologic tindings and because fever in Laennec’s cirrhosis seems to occur in patients with severe clinical signs (jaundice, hepatomegaly, and fluid retention)‘,’ the tendency to attribute fever to abnormal liver enzymes is probably, more often that not, a mistake. Seizures and alcohol withdrawal have both been shown to cause fever in the absence of other identifiable causes.8-1o It has also been shown that, in both situations, concomitant infections, particularly pneumonias, are common.‘*4 A total of 14 patients were thought to be in some stage of alcohol withdrawal. Withdrawal, with or without seizures, was commonly accompanied by multiple other potential causes of fever as has been reported by others.’ The other causes included pneumonia (6), urinary tract infection (I), a leg abscess (l), pancreatitis (2), rhabdomyolysis (2), alcoholic liver disease (l), an upper respiratory tract infection (l), and a suspected viral syndrome (1). Volume depletion has been implicated as a cause of fever in alcohol withdrawal and the fever often resolves after volume repletion alone.4 Only 4 of the 14 patients with the alcohol withdrawal syndrome had no other significant cause of fever noted. Of interest is the fact that no cases of occult central nervous system infections were discovered despite the fact that fever and altered mental status coexisted in six patients in the absence of another identifiable cause of fever. In all six cases, the lumbar puncture showed sterile cerebrospinal fluid (CSF). In one case, bloody CSF was the clue to a subarachnoid hemorrhage. In another patient with seizures,
26k -
22k ”
18k-
s
14klOk6k -
Infected (mean 11.1) (range 3.9k-29k)
Noninfected (mean 9.9) (range 4.0k- 16.5k)
FIGURE 2. WBC in febrile alcoholics.
60
AMERICAN
JOURNAL
a mildly elevated protein (71 mg/dL) was seen with a traumatic tap (600 red blood cells [RBCs] and no WBCs in tube 1 and 20 RBCs and no WBCs in tube 4). Despite these negative findings, we agree with the statement “confusion or obtundation in alcoholic patients . . . should never be attributed to toxicity associated with infection, alcoholism, or hepatic decompensation, until meningitis has been ruled out by lumbar puncture. ” The initial history and physical examination in the alcoholic may be particularly unreliable in guiding the clinician to the correct diagnosis. In several cases symptoms pointed to one organ system while the infection was found in a different organ system. Alcoholics may also harbor more than one focus of infection. One patient had four concomitant infections (pneumonia, trichomonas vaginitis, perirectal abscess, and UTI). CONCLUSIONS The alcoholic is predisposed to fever from a vast array of causes. In summary, the following points can be made. Alcoholics present with multiple problems, many of which can cause fever. Both infectious and noninfectious causes may coexist and multiple infections may coexist. Commonly used clinical parameters like the WBC and degree of temperature elevation are not practical ways to differentiate infectious from noninfectious causes. Noninfectious causes were often, in and of themselves, sufftcient to warrant admission in this series. The initial history was often incomplete and misleading. The most common infection in this study was pneumonia with characteristic or diagnostic clinical features developing after admission. Pneumonia also commonly developed in a setting known to predispose to alteration in mental status
OF EMERGENCY
MEDICINE
W Volume
9, Number
1 n January
1991
(for example seizures). There was often poor correlation between physical findings and roentgenogram. UTIs were not as rare in this series as in others and were often unsuspected. The most common noninfectious cause of fever was alcohol withdrawal with or without seizures. Clinically diagnosed alcoholic hepatitis probably only occasionally causes fever. There is a necessity to maintain a high index of suspicion and a low threshold for diagnostic testing and treatment; repeat examinations need to be performed and observation in the hospital is often necessary. REFERENCES 1. Tavel ME, Davison W, Batterton TD: A critical analysis of mortality associated with delerium tremens-Review of 39 fatalities in a nine-year period. Am J Med Sci 1961;242:18-29 2. Tisdale WA, Klatskin G: The fever of Laennec’s cirrhosis. Yale J Biol Med 1960;33:94-106 3. McFarland W, Libre EP: Abnormal leukocyte response in alcoholism. Ann Intern Med 1963;59:865-877 4. Rose HD, Golbert TM, Sanz CZ, Leitschuh TH. Fever during acute alcohol withdrawal. Am J Med Sci 1970;260:112-121 5. Shulman JA, Phillips LA, Petersdorf RG: Errors and hazards in the diagnosis and treatment of bacterial pneumonias. Ann Intern Med 1965;62:41-58 6. Nungester WJ, Klepser RG: A possible mechanism of lowered resistance to pneumonia. J Infect Dis 1938;63:94-102 7. Sherlock S: Alcoholic liver disease: Clinical patterns and diagnosis. Acta Med Stand 1985;703:103-110 (suppl) 8. Wachtel TJ, Steele GH, Day JA: Natural history of fever following seizure. Arch Intern Med 1987;147:1153-1155 9. lsbell H. Fraser HG. Wikler A. et al: An experimental study of the etiology of “rum fits” and delirium tremens. Quart J Stud Alcohol 1955;16:1-33 10. Thompson WL, Johnson AD, Maddrey WL, et al: Diazepam and paraldehyde for treatment of severe delirium tremens. Ann Intern Med 1975;82:175-180 11. Carpenter RR, Petersdorf RG. The clinical spectrum of bacterial meningitis. Am J Med 1962;33:262-275
