CORRESPONDENCE
tal experience of any single physician or studies containing a small number of patients detailing the safety of upper airway manipulation/visualization in the ED are convincing evidence that such manipulation is unif o r m l y safe. We p r e f e r to a w a i t published, peer-reviewed verification of the safety of direct visualization by these procedures in large numbers of children before we entirely discard radiography and initially perform visualization procedures on all children with suspected epiglottitis. Instead, we believe that radiography should be the initial procedure performed on stable children with a low or moderate suspicion of epiglottitis. If radiographs reveal an enlarged epiglottis , patients should be treated as having classic epiglottitis and taken by a team directly to the operating room. This approach will avoid needless and potentially hazardous airway manipulation in the ED by tongue blade, indirect laryngoscopy, o r flexible laryngoscopy. Stable children with normal radiographs should have their epiglottis visualized in the ED by a physician skilled in airway management to rule out "normal radiograph" epiglottitis. Because the majority of children with epiglottitis have diagnostic radiographs, I° only a small number of children who truly have epiglottitis will be subjected to visualization procedures in the ED. In conclusion, we believe that radiographs can contribute to the diagnosis of epiglottitis and are appropriate in patients with stable o r n o n "classic" presentation when used in a context similar to that described above. Until large prospective studies prove that indirect laryngoscopy, tongue blade visualization, and other airway visualization procedures are uniformly safe in patients (especially children) with epiglottitis, we believe that radiographs will c o n t i n u e to play an important role in the diagnosis of this disease. When radiographs are obtained, we believe that the criteria described in our study will assist physicians in interpreting these films.
Steven G Rothrock, MD Ronald M Howard, MD 158/439
Department of Emergency Medicine Loma Linda University Medical Center Loma Lind& California 1. Rosen P, Baker FJ, Barkin RM, et al: Emergency Medicine: Concepts and clinical practice, ed 2. St Louis~ CV Mosby, 1988, p 2232-2236. 2. Tintinalli JE, Krome RL, Ruiz E: Emergency Medicine: A Comprehensive Study Guide, ed 2. New York, McGraw Hill, 1988, p 592-594. 3. Barkin P,M, Rosen P: Emergency Pediatrics, ed 3. St Louis, CV Mosby, 1990, p 636-644. 4. Fleischer G, Ludwig S: Textbook of Pediatric Emergency Medicine, ed 2. Baltimore, Williams & Wilkins, 1988, p 435-438. 5. Ehrlich FE, Heldrich FJ, Tepas JJ: Pediatric Emergency Medicine, ed 1. Rockville, Aspen Publishers, 1987, p 55 57. 6. Mayosmith M•, Hirsch pJ, Wodzinski SF, et al: Acute epiglottitis in adults: An eight year experience in the state of Rhode Island. N Eng] J Med 1986;314:1133-1139. 7. Losek TD, Dewitz-Zink BA, Melzer-Lange M, et al: Epiglottis: Comparison of signs and symptoms in chii dren less than 2 years old and older. Ann Ernerg Med 1990;19:55-57. 8. Baxter J: Acute epiglottitis in children. Laryngoscope I967;77:1358-1367. 9. Mauro RD, Poole SR, Lockhart CH: Differentiation of epiglottitis from laryngotracheitis in the child with stridor. A m J Dis Child 1988;142:678-682. 10. Hodge KM, Ganzel TM: Diagnostic and therapeutic efficiency in croup and epiglottitis. Laryngoscope 1987;97:621-625.
Closed Thoracic Cavity Lavage For Hypothermia With Cardiac Arrest To the Editor: In their paper, "Closed Thoracic Cavity Lavage in the Treatment of Severe Hypothermia in H u m a n Beings" [February 1990;19:204-206] Drs Hall and Syverud presented two interesting cases in which active core rewarming was achieved using chest tubes for continuous pleural lavage. They speculated that the true efficacy of this technique will not be known until it can be attempted in patients suffering from pure environm e n t a l l y induced h y p o t h e r m i a uncomplicated by other conditions. I present a case of successful resuscitation from severe hypothermia in an alcoholic patient with underlying diabetic ketoacidosis and Gram-negative sepsis. A 49-year-old man was brought to the hospital after being found unresponsive on a cold floor. Paramedics initially found weak carotid pulses Annals of Emergency Medicine
and s p o n t a n e o u s r e s p i r a t i o n s of eight. The cardiac monitor showed a sinus bradycardia at a rate of 32. Fingerstick blood sugar was 600 mg/dL. The patient was intubated and transported by ambulance. En route to the hospital, his r h y t h m deteriorated into ventricular fibrillation and defibrillation was attempted four times w i t h o u t success. CPR was in progress when the patient arrived in the emergency department. The patient's initial core temperature was 25.5 C by rectal probe. At this time, the cardiac monitor showed fine ventricular fibrillation. IV infusion of atropine, epinephrine, and lidocaine and repeated attempts at defibrillation were unsuccessful. Partial cardiopulmonary bypass was n o t available at our institution; consequently, a single 40-F thoracost o m y tube was placed in the left fourth intercostal space for infusion of warm, normal saline (35 C). After 1 L was infused, the chest tube was c o n n e c t e d to s u c t i o n ( P l e u r e v a c A-4005 ®, Deknatel, Fall River, Massachusetts). When most of the liter had been recovered, another liter of was saline was infused through the chest tube. In this manner, pleural lavage with 3 L of warm normal saline was achieved over about 14 minutes, with a subsequent increase in rectal temperature to 26.1 C. At this point, spontaneous Conversion to atrial fibrillation occurred with a rate of 50 to 80 and blood pressure of 75/35 m m Hg. Further w a r m pleural lavage by a single c h e s t t u b e was c o n t i n u e d along w i t h w a r m e d IV fluids and b l a n k e t s . A p p r o x i m a t e l y 20 L of warm saline were used for lavage. P,J:ter one and one-half hours the patient's rectal temperature increased to 31.1 C. Initial arterial blood gas showed a pH of 6.98; Pco2, 20 m m Hg; and Po2, 346 m m Hg. Serum sodium was 155 mEq/L; potassium, 4.6 mEq/L; chloride, 114 mEq/L; COz, 7.3 mEq/ L; and glucose, 1,124 mg/dL. Vasopressors, insulin, and antibiotics also were used in the acute phase. Initial blood cultures grew Klebsiefla pneumoniae. The patient's hospital course was complicated by right 20:4 April 1991
CORRESPONDENCE
lobar pneumonia, rhabdomyolysis, and renal insufficiency, but he was discharged 17 days after admission with no neurologic deficits. There were no complications attributed directly to the pleural lavage. It should be emphasized that spontaneous resolution of our patient's ventricular fibrillation occurred well before a significant rise in general core t e m p e r a t u r e , s u p p o r t i n g the concept that direct warming of the heart is advantageous in the resuscitation of the severely hypothermic patient with life-threatening dysrhythmias refractory to conventional treatment. In situations in w h i c h partial c a r d i o p u l m o n a r y bypass is not available, closed thoracic cavity lavage presents an effective alternative method of active core rewarming. In addition to its ease of application, o u r method of active core rewarming using a single chest tube with bolus pleural lavage has the theoretical advantage of maximum heat exchange per liter of solution because the full liter is placed in the hemithorax, maximizing surface area exposure (in particular, cardiac surface area exposure) prior to evacuation. We continue to use this technique in the t r e a t m e n t of the sev e r e l y h y p o t h e r m i c p a t i e n t . We believe its near universal availability, ease of application, and excellent ability to rapidly rewarm the heart warrants its consideration as a treatment of severe hypothermia in selected patients when cardiopulmonary bypass is not available.
David T Walters, MD Department of Emergency Medicine Kern Medical Center Bakersfield, California
Verifying Dose Response To the Editor: Defining the vasopressor response to different doses of epinephrine is an i m p o r t a n t step in d e t e r m i n i n g whether "high-dose" epinephrine is of benefit during CPR. The methodology used by Gonzalez and colleagues in their paper, "Dose-Dependent Vasopressor Response to Epi20:4 April 1991
n e p h r i n e D u r i n g CPR in H u m a n Beings" [September 1989;18:920-926] involved the administration of repeated, increasing doses of epinephrine. This study design should be used cautiously in clinical trials so that results are not misinterpreted. Selection of the appropriate time interval between doses is critical in ensuring that effects seen are due to the last dose, rather than secondary to the cumulative effect of all doses given. 1,2 The magnitude and duration of a drug's effect with repeated administration is determined by the agent's p h a r m a c o k i n e t i c profile; the relationship between drug dose, plasma concentration and pharmacologic effect; and the time interval between doses. When a second, equal dose is administered subsequent to the complete elimination of the first dose, the effect seen is greater than that of the first dose. ~ As Levy succinctly discusses, this appears to be more significant with drugs that have a large volume of distribution. The effect can increase with each of the first four equal doses. A drug with a small volume of distribution may reach p h a r m a e o k i n e t i c and pharmacologic equilibrium after the second dose. 1 The five-minute dosing interval selected by Gonzalez et al was based on current advanced cardiac life support recommendations and epinephrine's short half-life in normal perfusion states. Information concerning e p i n e p h r i n e ' s e l i m i n a t i o n during CPR w o u l d be more appropriate; however, it is unavailable. Baseline plasma epinephrine concentrations are elevated after cardiac arrest. 3 In patients undergoing CPR, plasma epinephrine concentrations remain elevated five minutes after epinephrine administration. 4 When the substance of interest is both administered as a drug and produced endogenously, extreme difficulty arises in determining the most appropriate interval between doses. The most valid method of verifying the dose response described by Gonzalez et al would be to randomize the order that the different epinephrine doses are administered. A Annals of Emergency Medicine
review of epinephrine use in CPR did not find studies that randomized the order of different IV e p i n e p h r i n e doses. The a d m i n i s t r a t i o n of one dose level to each subject or prolonging the time interval between doses to 30 minutes, designs used in animal models,5, 6 are probably not reasonable in human studies. Investigators and readers of clinical trials should be aware of the phen o m e n o n of increasing drug effect with repeated dose drug administration. Study designs should be assessed to determine whether the information required to accurately select the time interval between doses has been considered. When the duration of pharmacologic effect does not allow for a prolonged period between d i f f e r e n t size d o s e s in c l i n i c a l studies, randomization of dosing order is necessary.
William A Watson, PharmD Janet Jordan, MD Department of Emergency Health Services School of Medicine University of Missouri-Kansas City Truman Medical Center 1. Levy G: Kinetics of pharmacologic effects. Clin PharmacoI Therap 1966;7:362-372. 2. Husain PJ, Watson WA, Runegin L, et al: A new model for evaluating lidocaine induced seizure activity (abstract). Anesthesiology 1984;6hA212. 3. Foley PF, Tacker WA, Wortsman J, et ah Plasma cateeholamine and serum cortiso] responses to experimental cardiac arrest in dogs. Am J PhysioI 1987;253: E283-289. 4. Quinton DN, O'Byrne G, Aitkenhead AR: Comparison of endotracheal and peripheral intravenous adrenaline in cardiac arrest. Lancet 1987~1:828-829. 5. Kosnik JW, Jackson RE, Keats S, et ah Dose-related response of centrally administered epinephrine on the change in aortic diastolic pressure during closed-chest massage in dogs. Ann Emerg Med 1985;14:204-208. 6. Ralston SH, Tacker WA, Showen L, et ah Endotracheai versus intravenous epinephrine during electromechanical dissociation with CPR in dogs. Ann Emerg Med 1985;14:1044-1048.
In Reply: We agree that randomization of the dosing order is scientifically appropriate when the pharmacological effect does not allow for a prolonged period b e t w e e n doses in clinical studies. However, early investigation of a promising new treatment often requires c o m p r o m i s e b e t w e e n the 440/159
tal experience of any single physician or studies containing a small number of patients detailing the safety of upper airway manipulation/visualization in the ED are convincing evidence that such manipulation is unif o r m l y safe. We p r e f e r to a w a i t published, peer-reviewed verification of the safety of direct visualization by these procedures in large numbers of children before we entirely discard radiography and initially perform visualization procedures on all children with suspected epiglottitis. Instead, we believe that radiography should be the initial procedure performed on stable children with a low or moderate suspicion of epiglottitis. If radiographs reveal an enlarged epiglottis , patients should be treated as having classic epiglottitis and taken by a team directly to the operating room. This approach will avoid needless and potentially hazardous airway manipulation in the ED by tongue blade, indirect laryngoscopy, o r flexible laryngoscopy. Stable children with normal radiographs should have their epiglottis visualized in the ED by a physician skilled in airway management to rule out "normal radiograph" epiglottitis. Because the majority of children with epiglottitis have diagnostic radiographs, I° only a small number of children who truly have epiglottitis will be subjected to visualization procedures in the ED. In conclusion, we believe that radiographs can contribute to the diagnosis of epiglottitis and are appropriate in patients with stable o r n o n "classic" presentation when used in a context similar to that described above. Until large prospective studies prove that indirect laryngoscopy, tongue blade visualization, and other airway visualization procedures are uniformly safe in patients (especially children) with epiglottitis, we believe that radiographs will c o n t i n u e to play an important role in the diagnosis of this disease. When radiographs are obtained, we believe that the criteria described in our study will assist physicians in interpreting these films.
Steven G Rothrock, MD Ronald M Howard, MD 158/439
Department of Emergency Medicine Loma Linda University Medical Center Loma Lind& California 1. Rosen P, Baker FJ, Barkin RM, et al: Emergency Medicine: Concepts and clinical practice, ed 2. St Louis~ CV Mosby, 1988, p 2232-2236. 2. Tintinalli JE, Krome RL, Ruiz E: Emergency Medicine: A Comprehensive Study Guide, ed 2. New York, McGraw Hill, 1988, p 592-594. 3. Barkin P,M, Rosen P: Emergency Pediatrics, ed 3. St Louis, CV Mosby, 1990, p 636-644. 4. Fleischer G, Ludwig S: Textbook of Pediatric Emergency Medicine, ed 2. Baltimore, Williams & Wilkins, 1988, p 435-438. 5. Ehrlich FE, Heldrich FJ, Tepas JJ: Pediatric Emergency Medicine, ed 1. Rockville, Aspen Publishers, 1987, p 55 57. 6. Mayosmith M•, Hirsch pJ, Wodzinski SF, et al: Acute epiglottitis in adults: An eight year experience in the state of Rhode Island. N Eng] J Med 1986;314:1133-1139. 7. Losek TD, Dewitz-Zink BA, Melzer-Lange M, et al: Epiglottis: Comparison of signs and symptoms in chii dren less than 2 years old and older. Ann Ernerg Med 1990;19:55-57. 8. Baxter J: Acute epiglottitis in children. Laryngoscope I967;77:1358-1367. 9. Mauro RD, Poole SR, Lockhart CH: Differentiation of epiglottitis from laryngotracheitis in the child with stridor. A m J Dis Child 1988;142:678-682. 10. Hodge KM, Ganzel TM: Diagnostic and therapeutic efficiency in croup and epiglottitis. Laryngoscope 1987;97:621-625.
Closed Thoracic Cavity Lavage For Hypothermia With Cardiac Arrest To the Editor: In their paper, "Closed Thoracic Cavity Lavage in the Treatment of Severe Hypothermia in H u m a n Beings" [February 1990;19:204-206] Drs Hall and Syverud presented two interesting cases in which active core rewarming was achieved using chest tubes for continuous pleural lavage. They speculated that the true efficacy of this technique will not be known until it can be attempted in patients suffering from pure environm e n t a l l y induced h y p o t h e r m i a uncomplicated by other conditions. I present a case of successful resuscitation from severe hypothermia in an alcoholic patient with underlying diabetic ketoacidosis and Gram-negative sepsis. A 49-year-old man was brought to the hospital after being found unresponsive on a cold floor. Paramedics initially found weak carotid pulses Annals of Emergency Medicine
and s p o n t a n e o u s r e s p i r a t i o n s of eight. The cardiac monitor showed a sinus bradycardia at a rate of 32. Fingerstick blood sugar was 600 mg/dL. The patient was intubated and transported by ambulance. En route to the hospital, his r h y t h m deteriorated into ventricular fibrillation and defibrillation was attempted four times w i t h o u t success. CPR was in progress when the patient arrived in the emergency department. The patient's initial core temperature was 25.5 C by rectal probe. At this time, the cardiac monitor showed fine ventricular fibrillation. IV infusion of atropine, epinephrine, and lidocaine and repeated attempts at defibrillation were unsuccessful. Partial cardiopulmonary bypass was n o t available at our institution; consequently, a single 40-F thoracost o m y tube was placed in the left fourth intercostal space for infusion of warm, normal saline (35 C). After 1 L was infused, the chest tube was c o n n e c t e d to s u c t i o n ( P l e u r e v a c A-4005 ®, Deknatel, Fall River, Massachusetts). When most of the liter had been recovered, another liter of was saline was infused through the chest tube. In this manner, pleural lavage with 3 L of warm normal saline was achieved over about 14 minutes, with a subsequent increase in rectal temperature to 26.1 C. At this point, spontaneous Conversion to atrial fibrillation occurred with a rate of 50 to 80 and blood pressure of 75/35 m m Hg. Further w a r m pleural lavage by a single c h e s t t u b e was c o n t i n u e d along w i t h w a r m e d IV fluids and b l a n k e t s . A p p r o x i m a t e l y 20 L of warm saline were used for lavage. P,J:ter one and one-half hours the patient's rectal temperature increased to 31.1 C. Initial arterial blood gas showed a pH of 6.98; Pco2, 20 m m Hg; and Po2, 346 m m Hg. Serum sodium was 155 mEq/L; potassium, 4.6 mEq/L; chloride, 114 mEq/L; COz, 7.3 mEq/ L; and glucose, 1,124 mg/dL. Vasopressors, insulin, and antibiotics also were used in the acute phase. Initial blood cultures grew Klebsiefla pneumoniae. The patient's hospital course was complicated by right 20:4 April 1991
CORRESPONDENCE
lobar pneumonia, rhabdomyolysis, and renal insufficiency, but he was discharged 17 days after admission with no neurologic deficits. There were no complications attributed directly to the pleural lavage. It should be emphasized that spontaneous resolution of our patient's ventricular fibrillation occurred well before a significant rise in general core t e m p e r a t u r e , s u p p o r t i n g the concept that direct warming of the heart is advantageous in the resuscitation of the severely hypothermic patient with life-threatening dysrhythmias refractory to conventional treatment. In situations in w h i c h partial c a r d i o p u l m o n a r y bypass is not available, closed thoracic cavity lavage presents an effective alternative method of active core rewarming. In addition to its ease of application, o u r method of active core rewarming using a single chest tube with bolus pleural lavage has the theoretical advantage of maximum heat exchange per liter of solution because the full liter is placed in the hemithorax, maximizing surface area exposure (in particular, cardiac surface area exposure) prior to evacuation. We continue to use this technique in the t r e a t m e n t of the sev e r e l y h y p o t h e r m i c p a t i e n t . We believe its near universal availability, ease of application, and excellent ability to rapidly rewarm the heart warrants its consideration as a treatment of severe hypothermia in selected patients when cardiopulmonary bypass is not available.
David T Walters, MD Department of Emergency Medicine Kern Medical Center Bakersfield, California
Verifying Dose Response To the Editor: Defining the vasopressor response to different doses of epinephrine is an i m p o r t a n t step in d e t e r m i n i n g whether "high-dose" epinephrine is of benefit during CPR. The methodology used by Gonzalez and colleagues in their paper, "Dose-Dependent Vasopressor Response to Epi20:4 April 1991
n e p h r i n e D u r i n g CPR in H u m a n Beings" [September 1989;18:920-926] involved the administration of repeated, increasing doses of epinephrine. This study design should be used cautiously in clinical trials so that results are not misinterpreted. Selection of the appropriate time interval between doses is critical in ensuring that effects seen are due to the last dose, rather than secondary to the cumulative effect of all doses given. 1,2 The magnitude and duration of a drug's effect with repeated administration is determined by the agent's p h a r m a c o k i n e t i c profile; the relationship between drug dose, plasma concentration and pharmacologic effect; and the time interval between doses. When a second, equal dose is administered subsequent to the complete elimination of the first dose, the effect seen is greater than that of the first dose. ~ As Levy succinctly discusses, this appears to be more significant with drugs that have a large volume of distribution. The effect can increase with each of the first four equal doses. A drug with a small volume of distribution may reach p h a r m a e o k i n e t i c and pharmacologic equilibrium after the second dose. 1 The five-minute dosing interval selected by Gonzalez et al was based on current advanced cardiac life support recommendations and epinephrine's short half-life in normal perfusion states. Information concerning e p i n e p h r i n e ' s e l i m i n a t i o n during CPR w o u l d be more appropriate; however, it is unavailable. Baseline plasma epinephrine concentrations are elevated after cardiac arrest. 3 In patients undergoing CPR, plasma epinephrine concentrations remain elevated five minutes after epinephrine administration. 4 When the substance of interest is both administered as a drug and produced endogenously, extreme difficulty arises in determining the most appropriate interval between doses. The most valid method of verifying the dose response described by Gonzalez et al would be to randomize the order that the different epinephrine doses are administered. A Annals of Emergency Medicine
review of epinephrine use in CPR did not find studies that randomized the order of different IV e p i n e p h r i n e doses. The a d m i n i s t r a t i o n of one dose level to each subject or prolonging the time interval between doses to 30 minutes, designs used in animal models,5, 6 are probably not reasonable in human studies. Investigators and readers of clinical trials should be aware of the phen o m e n o n of increasing drug effect with repeated dose drug administration. Study designs should be assessed to determine whether the information required to accurately select the time interval between doses has been considered. When the duration of pharmacologic effect does not allow for a prolonged period between d i f f e r e n t size d o s e s in c l i n i c a l studies, randomization of dosing order is necessary.
William A Watson, PharmD Janet Jordan, MD Department of Emergency Health Services School of Medicine University of Missouri-Kansas City Truman Medical Center 1. Levy G: Kinetics of pharmacologic effects. Clin PharmacoI Therap 1966;7:362-372. 2. Husain PJ, Watson WA, Runegin L, et al: A new model for evaluating lidocaine induced seizure activity (abstract). Anesthesiology 1984;6hA212. 3. Foley PF, Tacker WA, Wortsman J, et ah Plasma cateeholamine and serum cortiso] responses to experimental cardiac arrest in dogs. Am J PhysioI 1987;253: E283-289. 4. Quinton DN, O'Byrne G, Aitkenhead AR: Comparison of endotracheal and peripheral intravenous adrenaline in cardiac arrest. Lancet 1987~1:828-829. 5. Kosnik JW, Jackson RE, Keats S, et ah Dose-related response of centrally administered epinephrine on the change in aortic diastolic pressure during closed-chest massage in dogs. Ann Emerg Med 1985;14:204-208. 6. Ralston SH, Tacker WA, Showen L, et ah Endotracheai versus intravenous epinephrine during electromechanical dissociation with CPR in dogs. Ann Emerg Med 1985;14:1044-1048.
In Reply: We agree that randomization of the dosing order is scientifically appropriate when the pharmacological effect does not allow for a prolonged period b e t w e e n doses in clinical studies. However, early investigation of a promising new treatment often requires c o m p r o m i s e b e t w e e n the 440/159
