Hyperpyrexia Complicating Low Fixed Cardiac Output

infection developed following fiberoptic bronchoscopic examination in an elderly man with severe congestive heart failure and moderate chronic renal insuffici~cy, but with no evident neoplastic disease. Harford10 demonstrated an increased susceptibility to inhaled pneumococci in mice with preexisting conditions associated with pulmonary edema. Subsequently, Austrian and Gold 11 reported an "unusually high" mortality in patients with pneumococcal pneumonia who had had preexisting cardiac disease and pulmonary ·edema. It has been postulated that fiberoptic bronchoscopic examination could serve as the means of inoculation, carrying the organisms from contaminated upper airways to the culturerich alveolar spaces.a It is possible that associated conditions, such as congestive heart failure, atelectasis, pulmonary emboli, and obstructing carcinoma, augment bacterial proliferation and the development of pneumonitis. Although fiberoptic bronchoscopic examination is a relatively safe diagnostic procedure in the hands of the experienced endoscopist, the course of events in the current case emphasizes that significant and occasionally fatal infectious complications may occur. ACKNOWLEDGMENTS: We wish to thank John A. Pierce, M.D. for his constructive criticism of the manuscript REFERENCES

1 Credle WF, Smiddy JF, Elliott RC: Complications of fiberoptic bronchoscopy. Am Rev Respir Dis 109:67, 1974 2 Timms RM, Harrell JH : Bacteremia related to fiberoptio bronchoscopy: A case report. Am Rev Respir Dis 111: 555,1975 3 Pereira W, Kovnat DM, Khan MA, et al : Fever and pneumonia after flexible fiberoptic bronchoscopy. Am Rev Respir Dis 112:59, 1975 4 Harvey WP, Capone MA : Bacterial endocarditis related to cleaning and filling of teeth with particular reference to the inadequacy of present day knowledge and practice of antibiotic phophylaxis for all dental procedures. Am J Cardiol7 :793, 1961 5 Lebrock J, Ellis CA, Klainer DS, et al : Transient bacteremia associated with barium enema. Arch Intern Med 135:835,1975 6 Radner DD: Postbronchoscopic reactions in pulmonary tuberculosis. Am Rev Tuberc 47:370, 1943 7 Titche LL: Postbronchoscopic reactions. Ann Otol 54: 568, 1945 8 Burman SO: Bronchoscopy and bacteremia. J Thorac Cardiovasc Surg 40:635, 1960 9 Kane RC, Cohen MH, Fossieck BE Jr, et al : Absence of bacteremia after fiberoptic bronchoscopy. Am Rev Respir Dis 111:102, 1975 10 Harford CC : Pulmonary edema in influenza pneumonia of the mouse and the relation of fluid in the lung to the inception of pneumococcal pneumoni~ . J Exp Med 91 : 245, 1950 11 Austrian R, Cold J : Pneumococcal bacteremia with special reference to bacteremia pneumococcal pneumonia. Ann Intern Med 60:759, 1964

CHEST, 72: 1, JULY, 1977

Hyperpyrexia Complicating Low Fixed Cardiac Output* Thomas]. Vander Salm, M.D.;•• John P. Howe, III, M.D.;t and ]ames E. Dalen, M .D ., F.C.C.P.;f:

A 41-year-old woman with end-stage mitn1 and aortic stenosis developed the cycle of low cardiac output, peripheral vasoconstriction, increased core tempenture, and cardiac decompeDSation. This was Interrupted by core cooling utilizing iced gastric lavage. We propose that her severe hyperthermia was caused or abetted by her low cardiac output. with fever is a well-recognized cause of hypoS epsis tension and reduced peripheral perfusion. Less commonly recognized is the converse syndrome, poor perfusion causing or abetting fever. The following case illustrates this syndrome and highlights the therapeutic difficulties of hyperpyrexia occurring in a patient with a low fixed cardiac output. CASE REPoRT

A 41-year-old woman was admitted to the University of Massachusetts Medical Center with progressive dyspnea of three week's duration. One year prior to the present admission, symptoms of orthopnea, exertional dyspnea, and peripheral edema had led to Cardiac catheterization at another hospital. These studies demonstrated mitral stenosis and aortic stenosis. Her Cardiac index was low at 1.8 L/min/m. Her pulmonary capillary wedge pressure was markedly elevated at 30 mm Hg, and there was pulmonary hypertension at systemic levels (pulmonary arterial pressure, 106/60 mm Hg; mean, 80 mm Hg). Double valve replacement was advised, but the patient declined. Three weeks prior to this admission, her biventricular failure became progressively worse. On the day of admission, the patient could not sleep because of severe dyspnea, and she had marked peripheral edema. Her medications were digoxin ( 0.25 mg daily), spironolactone ( 25 mg three times daily), and furosemide ( 40 mg twice daily) . On examination, the patient's respiration rate was 30/min, her pulse rate was 112 beats per minute and regular, her blood pressure was 120/60 mm Hg, and her temperature was 36.6"C (97.9"F). She waS diaphoretic and dyspneic while sitting. The patient's neck veins were distended to the angle of her jaw while sitting, with V -waves present. Bibasilar rales were present. The patient had decreased breath sounds and dullness to percussion over the lower one-half of her right hemithorax. She had a collapsing pulse, a right and left ventricular heave, and a gallop rhythm with a third heart sound. A grade 3/6 systolic murmur at the apex radiated to the left axilla and a grade 2/6 systolic murmur at °From the Departments of Surgery, Medicine, and Cardiovascular Medicine, University of Massachusetts Medical Center, Worcester. 0 0 Assistant Professor of Surgery. tV ice Chairman, Department of Medicine. :!:Professor and Chairman, Department of Cardiovascular Medicine.

HYPERPYREXIA COMPUCATING LOW FIXED CARDIAC OUTPUT 107

the base radiated to the neck. A diastolic decrescendo murmur was heard at the left sternal border. The patient's liver was enlarged, pulsatile, and tender. Pitting ankle edema ( 4 + ) was present. LoboratOf'IJ Data

The results of laboratory investigations were as follows: hematocrit reading, 46 percent; white blood cell count (WBC), 15,600/cu mm; differential count, 1 band cell, 87 segmented cells, 10 lymphocytes, and 2 monocytes; blood urea nitrogen level (BUN), 33.5 mg/100 ml; and bilirubin leve~ 2.5 mg/100 mi. Three cultures of blood were negative. The chest x-ray film showed pulmonary edema, biventricular enlargement, and a right pleural effusion. The patient's electricardiogram showed right ventricular hypertrophy, left axis deviation, and normal sinus rhythm. A tuberculin test with purified protein derivative of tuberculin was negative. H08Pital Course

With diuresis, therapy with digoxin, and bed rest, the patient's congestive heart failure improved, and she lost 4.5 kg ( 10 lb) over one week. A first thoracocentesis yielded 500 ml of thiclc bloody fluid, and a second, two days later, yielded 1,225 ml of thiclc bloody fluid. A biopsy of the pleura using a Cope needle showed chronic inflammation. The cytologic findings on the pleural fluid were class 3 ( suspicious), and the culture was negative. Laboratory values for the pleural fluid were as follows: protein level. 3.6 gm/100 ml; glucose level, 95 mg/100 ml; WBC, 4,600/cu mm; and red blood cells count. 350,000/cu mm. The chest x-ray film after thoracocenblsis showed a diffuse opacity in the right lower pulmonary field, with a small amount of remaining fluid. On the basis of these data, a tumor as the cause of the bloody pleural effusion could not be excluded. Therefore, fiberoptic flexible bronchoscopy examination under topical anesthesia was performed. No abnormalities were seen. Washings yielded no findings indicative of a tumor. Shortly after the bronchoscopic examination, the patient developed increasing left and right ventricular failure. An ECG demonstrated junctioilal rhythm with a rate of 120 beats per minute. The patient's temperature was noted to be 40• ( 104•F). Cultures of blood, urine, and sputum were obtained (all were negative, except for rare Stophylococcw aureua in sputum). Therapy with cephalothin (Kellin) sodium and gentamicin were begun. Despite therapy with aspirin, use of a cooling blanlcet, and sponging with alcoho~ the patient's temperature rose progressively over four hours to 42.8•C ( 109•F) ( checlced repeatedly with different thermometers) . Respiratory failure required intubation and positive-pressure ventilation. The patient's pulse rate rose to 150 beats per minute, her blood pressure dropped to 70/50 mm Hg, and her production of urine fell to zero, despite intravenous administration of 120 mg of furosemide. The patient was semicomatose. Despite a temperature of 42.S•c, the patient's slcin was cool and clammy. In order to remove heat, we lavaged her stomach with iced glucose (dextrose) solution. Within onehalf hour, the patient's temperature had dramatiCally fallen to 38•c ( 100.4.F), her cardiac rhythm reverted to normal sinus rhythm at 100 beats per minute and simultaneously, her output of urine increased.

Therapy with dopamine was started ( 40p.g/min) and

108 VANDER SALM, HOWE, DALEN

was continued until the next day. For four days the patient's temperature varied between 36.6•C and 38.3•C (97.9•F to 100.9"F) and then became normal. Repeated cultures of blood were negative. The patient's BUN rose to a peale of 114 mg/100 ml, which then fell baclc to 47 mg/100 ml (creatinine level rose to 3.3 mg/100 ml and then fell baclc to 1.1 mg/100 ml). The patient subsequently underwent successful aortic and mitral valve replacement. DISCUSSION

The patient we have described presented a difficult diagnostic and therapeutic dilemma. Although bronchoscopic examination can be associated with low-grade temperatures, no description of such excessive fever ( 42.s•c) could be found.1.2 Cultures did not identify a cause for fever. Malignant hyperthermia may occur after general anesthesia and is associated with severe metabolic acidosis, neither of which was present in this case. Therapy with atropine, this patient's premedication, has been associated with fever but only when administered in large doses.a Cocaine, the topical anesthesia ( 4 ml of a 4 percent solution) used in this patient, may be pyrogenic;a however, the total dosage ( 160 mg) used was below the accepted "safe" limit for this drug.• Thus, no clear cause for the patient's fever emerges. However, it is possible that the low cardiac output and peripheral vasoconstriction in this patient led to retention of heat and increasing fever. What is the evidence to support this chain of events? Transfer of heat between two objects is proportional · to the temperature gradient between them. As the temperature of the skin rises, more heat is transferred to the environment; as the temperature of the skin falls, less heat is transferred (assuming a constant environmental temperature) . On the basis of thennodynamics, it is clear that increased production of heat by the body demands either an increased transfer to the environment or an elevation in the body temperature. The fonner phenomenon is the nonnal response. Badder et alii documented this using, as a heat source, amino acid infusions in nonnal humans. The response was an unchanged core temperature and an increase in the forehead (peripheral) temperature from 32.2"C (90"F) to 34.7"C (94.5"F). To supply. this vasodilated bed, the cardiac output rose from 5 L/min to 6.3 L/min. Yet the patient here was in shock. Since hypoperfusion causes ~ripheral vasoconstriction and a decreased temperature of the skin, there is an obligatory decrease in the transfer of heat to the environment. Conversely, dissipation of heat requires peripheral vasodilatation and an increased temperature of the skin. Thus, hypoperfusion could, by limiting the transfer of heat from the body, cause central or core hyperthennia. Studies by Ross et al, 8 by Spitzer and Brock,7 and by Hardaway8 have all described such a phenomenon. In the report of Ross et al,8 one of the patients with postoperative hypc>volemia demonstrated a modest rise fu core temperature to 39"C ( 102.2"F). When surface

CHEST, 72: 1, JULY, 1977

cooling was attempted, the peripheral temperature fell as the central temperature rose to 4l"C ( 105.~~F). Only after peripheral vasodilatation was achieved · did the central temperature fall. In the report by Spl&er and Brock, 7 the patient was a 25-year-old Welsh master butcher who underwent an aortic valve replacement. His postoperative course was complicated by high core temperatures ( 41.2"C; 106.2"F) low peripheral temperature ( 19"C; 66.2"F), neurologic deterioration, and hypovolemia. Treatment with volume expansion and chlorpromazine was totally successful, both in reducing the patient's temperature to normal and in reversing his neurologic deterioration. In the patient described herein, we propose that the extremely high fever was caused by the following pathophysiologic cascade: hronchoscopic examination induced her junctional rhythm, either directly or in conjunction with a low-grade fever caused by one of the previously mentioned sources. The junctional rhythm caused a further decrease in the patient's cardiac output which, in turn, caused poor peripheral perfusion and vasoconstriction. As the temperature of her skin fell, the patient was able to transfer less heat to the environment. This resulted in a rise in core temperature. This increase in the central temperature demanded an increased cardiac output, a demand that the patient could not meet because of her severe mitral stenosis, aortic stenosis, and junctional rhythm. Florid left and right ventricular failure ensued, causing a further drop in cardiac output and peripheral perfusion, thus completing the vicious cycle. As might he predicted, surface cooling did not alter the deterioration in the patient's condition. · In patients with high core temperatures caused or perpetuated by peripheral hypoperfusion, therapy with volume expansion and pharmacologic vasodilatation is usually successful. In this patient, increasing the perfusion by giving volume expanders was unappealing in the face of florid pulmonary edema. So, too, was giving a vasodilator drug in the presence of uncorrected shock. The break in the previously outlined cycle came rather dramatically by achieving core cooling with iced lavage of the patient's stomach. Her pulse rate fell pari passu with her temperature, and as sinus rhythm reappeared, her blood pressure and output of urine increased. In the occasional patient with hyperpyrexia and a fixed low cardiac output such as described herein, the options of administering volume expanders or vasodilator drugs, or both, may not he available. In such a case, core cooling may he valuable in interrupting the progressive cycle of fever and shock. In this case, iced gastric lavage was used, but cooling could also be performed via the peritoneal cavity (cold dialysis), colon (iced enemas), or blood ( extracorporeal circulation).

Dis 112:59, 1975 3 Goodman LS, Gilman A: The Pharmacological Basis of Therapeutics. New York, Macmillan Publishing Co, Inc, 1965 4 Dripps, RD, Eckenhoff JE, Vandam LD: Introduction to Anesthesia. Philadelphia, WB Saunders Co, 1963 5 Badder E, Gusberg RJ, Gump FE, et al: Circulatory requirements for heat tranSPort. Surg Forum 24:90, 1973 6 Ross BA, Brock Lord, Aynsley-Green A: Observations on central peripheral temperatures in the understanding and management of shock. Br J Surg 56:887, 1969 7 Spitzer AG, Brock Lord: The reoognition of hypovolemia after open heart surgery. Guys HOSP Rep 117:131, 1968 8 Hardaway RM III: Clinical Management of Shock, Surgical and Medical. Springfield, Ill, Charles C Thomas, 1968

Myocardial Infarction Associated with Thyrotoxicosis* A . ]. Proskey, M.D.; Franklin Saksena, M.D.; and WiUiam D. Towne, M.D., F.C.C .P.

Myocardial infarctioo ocean l'llftly with thyrotosicosis. A 34-year-old woman with thyrotosicosis sustained a transmural myocardial infan:tion and subsequently ou cardiac catheterlzatiou studies bad uo significant coroD8l)' arterial disease but only residual apical wall akinesia. Thyroid hormone may diredly inftuenc:e myocardial oxygen supply and demand and, by some unknown mech• nism eiclusive of major coroD8l)' arterial blood supply, cause a critical Imbalance resulting In angiDa pectoris and myocardial infarction. angina pectoris occurs occasionally in paAlthough tients with thyrotoxicosis, myocardial infarction has been reported rarely. 1 In both instances, underlying atheromatous coronary disease has been presumed present as the cause. 2 Although the physiologic effects of thyroid hormone on the cardiovascular system are well documented, 8 little is known about the potential direct deleterious effect of excessive thyroid hormone on the heart in the absence of apparent heart disease. The purpose of this report is to describe the case of a young woman presenting with \instable angina pectoris and active thyrotoxicosis who sustained a transmural myocardial infarction and who, on subsequent cardiac catheterization studies, had no significant coronary disease hut only apical wall akinesia as a result of the past myocardial infarction.

CASE REPoRT The patient, a 34-year-old woman, was admitted via the emergency room on June 14, 1975, because of severe retro-

1 Bunnan SO, Hill M: Bronchoscopy and bacteremia. Thorac Cardiovasc Surg 40:635, 1960 2 Pereira W, Kovnat DM, Khan MA, et al: Fever and pneumonia after flexible fiberoptic bronchoscopy. Am Rev ReSPir

CHEST, 72: 1, JULY, 1977

From the Division of Adult Cardiology, Department of Medicine, Coole County HOSPital, Northwestern University, and Loyola University, Chicago. Reprint requests: Dr. Proskey, Dit>i.tion of Adult Cardiology, 1835 West Harrison, Chicago 60612 0

MYOCARDIAL INFARCnON ASSOCIATED WITH THYROTOXICOSIS 109