The Pathophysiology of Smoke Inhalation In jury S. FRED STEPHENSON, B.S., BARRY C. ESRIG, M.D., HIRAM C. POLK, JR., M.D., ROBERT L. FULTON, M.D.
The consequences of near-lethal smoke inhalation in dogs were studied for a 72-hour period following injury. Progressive hypoxemia and decrease in compliance developed. Severe respiratory distress and frank pulmonary edema were not encountered. Respiratory insufficiency was related more to alterations in ventilation perfusion ratios than to alveolar destruction. These data were related to clinical observations made by others. No deterioration of lung function was seen with crystalloid overload imposed upon smoke inhalation. The presence of bacterial infection in dogs surviving beyond 24 hours appears pathogenically significant.
cARBON MONOXIDE and smoke poisoning are the major causes of early death resulting from fire.'9 Although many people die within minutes of the fire, some suffering the effects of smoke inhalation reach the hospital. Not infrequently, smoke inhalation is the only injury sustained by the victim. If the patient has sustained cutaneous thermal injury, the respiratory state is complicated by severe hypovolemic shock, massive tissue destruction, large volume fluid therapy, and infection. Compared to the magnitude of the problem of thermal injury and concomitant smoke inhalation in the United States,12"19 relatively little is known about the pathophysiology of uncomplicated smoke inhalation. To date, it is not possible to separate the respiratory effects of inhalation injury from the ventilatory effects of shock, massive fluid therapy, burn wound toxins, and sepsis. Laboratory studies have failed: 1) to establish the basic mechanisms responsible for respiratory failure from Submitted for publication June 5, 1975. Presented at American Burn Association meeting, March 20, 1975, Denver, Colorado. Reprint requests: R. L. Fulton, M.D., Department of Surgery, University of Louisville School of Medicine, Health Sciences Center, Louisville, Kentucky, 40201.
From the Price Institute of Surgical Research, and the Department of Surgery, University of Louisville School of Medicine, Health Sciences Center, Louisville, Kentucky
smoke inhalation; 2) to divorce the effects of thermal injury entirely from inhalation injury; 3) to establish a time-course of pulmonary function following injury; 4) to separate upper airway injury from lung injury; and 5) to establish the role of bacterial infection in the development of pulmonary failure following smoke inhalation. Most studies employ tracheal intubation to mimic the clinical picture of smoke inhalation through an intact respiratory tract. Although this laboratory technique may make the experimental injury numerically standard, it does not allow for the wide variation in lung injury observed clinically. From laboratory and clinical experience, Stone and co-workers'3"17 have staged inhalation injury into three temporal phases: 1) respiratory insufficiency occurring in the 24-36 hours after injury, 2) pulmonary edema occurring after 8 hours, and 3) bacterial pneumonia as a late stage. A laboratory model was sought which would simulate such a picture. The model devised would have to allow smoke inhalation through an intact airway to the point of near asphyxiation, sequential measurement of cardiovascular and pulmonary function, temporal evaluation of lung disease, and be useful for measurement of pulmonary effects of simultaneous smoke inhalation and other potential pulmonary insults, such as crystalloid infusion and aspiration of bacteria. Based on the study by Zikria and colleagues,'8 such a model was established using wood smoke and the dog. It was found that: 1) pulmonary function deteriorated for
652
Vol. 182 * No. 5
653
SMOKE INHALATION INJURY
4-24 hours following injury, but that treatment-resistant insufficiency rarely developed in this time period; 2) pulmonary edema was an inconsistent finding; 3) crystalloid "overload" had no effect upon the injury; 4) cardiovascular dysfunction was as profound as respiratory dysfunction; and 5) bacterial pneumonia was the most important limiting factor to survival. Methods Mongrel dogs weighing between 12 and 31 kg were given intravenous pentobarbital (30 mg/kg), and the trachea was intubated. Systemic arterial catheterization was performed through the femoral artery for measurement of mean arterial pressure (MAP) and arterial blood gases. A Swan-Ganz catheter was passed through a jugular vein into the pulmonary artery for determination of pulmonary artery pressure (PAP), wedge pressure (PWP), and retrieval of mixed venous blood. The endotracheal tube was then connected to a Collins spirometer for spirometric measurements (Tables 1 and 2). After initial variables were obtained, the endotracheal tube was removed, and the dogs were allowed to inhale wood smoke spontaneously from a specially designed apparatus. This apparatus enclosed only the dog's head. A wood fire was ignited in a remote combustion chamber, and
TABLE 1. Methods of Determination
Variable
Method of Measurement
Blood gases (Po,, Pco,, pH) V02 (oxygen consumption) Tidal volume Respiratory rate Expired CO2 Hemoglobin Vascular pressures
IL blood gas analyzer Collins' spirometer (5 minutes) Collins' spirometer Collins' spirometer Beckman medical gas analyzer Cyanmethemoglobin method Beckman dynograph and Statham strain gauges Harvard respirator (5 breaths)
Compliance5 Lung weight Lung per cent water
Weighing See text
Fourteen dogs were sacrificed at 4 hours for determination of weights, per cent of water and histologic examination of the lungs. Twelve dogs were sacrificed at 24 hours for similar data (one dog died on induction of anesthesia at 24 hours). Five dogs were scheduled to survive for 72 hours; however, two died between 48 and 72 hours. The latter seventeen dogs were extubated after 4 hours. Repeat anesthesia was necessary for the 24- and 72-hour measurements with recannulation of vessels and re-insertion of endotracheal tubes. In the event of death, anatomic data were recovered as soon as possible. Lung cultures were made from all the dying dogs. In 8 dogs, a crystalloid load of 10 mEq Na/kg (74.1 cc/kg) as Ringer's lactate was given in the 4 hours following smoke inhalation. Physiologic and anatomic variables were compared with the dogs sacrificed at 4 hours. Histologic examination was made of segments of several lobes from all dogs. The tissue was fixed in 10o formalin, inbedded in parafin and stained with hematoxylin and eosin.
smoke was conducted into the chamber containing the dog's head. With the temperature of the chamber being monitored (47.3 + 4.9 C), the dogs inhaled smoke for 5½-6 minutes. An 8-minute period of smoke inhalation was uniformly fatal. The dogs were removed from the chamber if bradypnea or apnea occurred. Most of the animals required immediate mechanical respiratory assistance to prevent death. Arterial blood gases obtained in the chamber were P02 36.7 + 11.0, PCo2 75.4 + 5.1 and Results pH 7.137 .026. Despite smoke inhalation to the point of near asphyxiaAt the end of the period of smoke inhalation, the dogs tion, no dog died before 4 hours, one dog of 12 died on were again intubated and immediately placed on 100%o induction of anesthesia at 24 hours and two of 5 died oxygen delivered by the Collins spirometer. After 30 between 48 and 72 hours. The two dying late had eviminutes the variables described in Tables 1 and 2 were dence of bacterial pneumonia. There was a significant determined. Percentage of water in the lung was obtained increase in lung weight at 4 hours as well as some inby taking small segments of the various lobes, weighing crease in lung water (Fig. 1). The changes in lung weight and drying to constant weight (3 days at 150 C). Then: ±
% H20
wet =
weight
-
dry weight
wet weight
TABLE 2. Calculated Variables
X 100
Oxygen consumption (V02) was determined after a 10-15 minute stabilization period of ventilation with 100o oxygen.
After the 30-minute measurements were taken, the animals were disconnected from the spirometer and allowed to breathe room air spontaneously until the next series of measurements. Determinations were obtained at 2, 4, 24 and 72 hours after injury.
Respiratory rate x tidal volume Expired Pco,-arterial Pco, arterial Pco, Fick Principle Cardiac output Blood 02 content ( [Hgb] x 1.34 x % 02 Sat.) + .0031 Po, Alveolar-arterial Po2gradientAlveolar Po,-arterial Po, (AA - a Poj) Alveolar P02 (Barometric pressure-47)-art. Pco2 Vascular resistance Arterial pressure-Vein pressure Cardiac output Minute volume Vd/Vt3
654
STEPHENSON AND OTHERS %
SURVIVAL
100
I7
80 60 A
l/2
C
4
2
722
24
LUNG WEIGHT gm/kg 18 r 16 -
14 12
-
-
_
InI
I
C 84
_
_
I
_
_
_
_
_
I
/2
2
_
Z
V
4
24
2
24
72
Ann. Surg. * November 1975
is shown by the increased respiratory rate and minute volume (Fig. 4). The animals continued to hyperventilate (increased minute volume) for at least 24 hours. The increased minute volume was primarily the result of increased tidal volume as rate tended to return to normal levels. Alterations in minute volume were not related to arterial P02 Pco2 or pH (Fig. 5). The ratio of dead space to tidal volume (Vd/Vt) was abnormal only at 30 minutes, returning rapidly to control values (Fig. 5). Cardiac output was decreased for the first 24 hours (Fig. 6). At 30 minutes the cardiac output was profoundly lowered, being less than one third of control. The lowered cardiac output was accompanied by slight but unsustained hypotension. Both systemic and pulmonary vascular resistance (Figs. 6 and 7) were substantially elevated for prolonged periods. Whereas MAP fell slight-
M 14-n
2
83 82 81
80 79
78
1'C '
1/2
'
2
'
{
4 HOURS
FIG. 1. (Top) No dog died within the first 4 hours after smoke inhalation. The only dog dying at 24 hours did so with the induction of anesthesia. The dogs dying at 72 hours died from pneumonia. (Center) Lung weights were elevated at 4, 24 and 72 hours after smoke inhalation. All elevations were statistically higher than normal. (Bottom) Lung per cent water was elevated at 4, 24 and 72 hours after smoke inhalation; however, gross pulmonary edema was unusual. *indicates statistically significant difference from control value (P
The consequences of near-lethal smoke inhalation in dogs were studied for a 72-hour period following injury. Progressive hypoxemia and decrease in compliance developed. Severe respiratory distress and frank pulmonary edema were not encountered. Respiratory insufficiency was related more to alterations in ventilation perfusion ratios than to alveolar destruction. These data were related to clinical observations made by others. No deterioration of lung function was seen with crystalloid overload imposed upon smoke inhalation. The presence of bacterial infection in dogs surviving beyond 24 hours appears pathogenically significant.
cARBON MONOXIDE and smoke poisoning are the major causes of early death resulting from fire.'9 Although many people die within minutes of the fire, some suffering the effects of smoke inhalation reach the hospital. Not infrequently, smoke inhalation is the only injury sustained by the victim. If the patient has sustained cutaneous thermal injury, the respiratory state is complicated by severe hypovolemic shock, massive tissue destruction, large volume fluid therapy, and infection. Compared to the magnitude of the problem of thermal injury and concomitant smoke inhalation in the United States,12"19 relatively little is known about the pathophysiology of uncomplicated smoke inhalation. To date, it is not possible to separate the respiratory effects of inhalation injury from the ventilatory effects of shock, massive fluid therapy, burn wound toxins, and sepsis. Laboratory studies have failed: 1) to establish the basic mechanisms responsible for respiratory failure from Submitted for publication June 5, 1975. Presented at American Burn Association meeting, March 20, 1975, Denver, Colorado. Reprint requests: R. L. Fulton, M.D., Department of Surgery, University of Louisville School of Medicine, Health Sciences Center, Louisville, Kentucky, 40201.
From the Price Institute of Surgical Research, and the Department of Surgery, University of Louisville School of Medicine, Health Sciences Center, Louisville, Kentucky
smoke inhalation; 2) to divorce the effects of thermal injury entirely from inhalation injury; 3) to establish a time-course of pulmonary function following injury; 4) to separate upper airway injury from lung injury; and 5) to establish the role of bacterial infection in the development of pulmonary failure following smoke inhalation. Most studies employ tracheal intubation to mimic the clinical picture of smoke inhalation through an intact respiratory tract. Although this laboratory technique may make the experimental injury numerically standard, it does not allow for the wide variation in lung injury observed clinically. From laboratory and clinical experience, Stone and co-workers'3"17 have staged inhalation injury into three temporal phases: 1) respiratory insufficiency occurring in the 24-36 hours after injury, 2) pulmonary edema occurring after 8 hours, and 3) bacterial pneumonia as a late stage. A laboratory model was sought which would simulate such a picture. The model devised would have to allow smoke inhalation through an intact airway to the point of near asphyxiation, sequential measurement of cardiovascular and pulmonary function, temporal evaluation of lung disease, and be useful for measurement of pulmonary effects of simultaneous smoke inhalation and other potential pulmonary insults, such as crystalloid infusion and aspiration of bacteria. Based on the study by Zikria and colleagues,'8 such a model was established using wood smoke and the dog. It was found that: 1) pulmonary function deteriorated for
652
Vol. 182 * No. 5
653
SMOKE INHALATION INJURY
4-24 hours following injury, but that treatment-resistant insufficiency rarely developed in this time period; 2) pulmonary edema was an inconsistent finding; 3) crystalloid "overload" had no effect upon the injury; 4) cardiovascular dysfunction was as profound as respiratory dysfunction; and 5) bacterial pneumonia was the most important limiting factor to survival. Methods Mongrel dogs weighing between 12 and 31 kg were given intravenous pentobarbital (30 mg/kg), and the trachea was intubated. Systemic arterial catheterization was performed through the femoral artery for measurement of mean arterial pressure (MAP) and arterial blood gases. A Swan-Ganz catheter was passed through a jugular vein into the pulmonary artery for determination of pulmonary artery pressure (PAP), wedge pressure (PWP), and retrieval of mixed venous blood. The endotracheal tube was then connected to a Collins spirometer for spirometric measurements (Tables 1 and 2). After initial variables were obtained, the endotracheal tube was removed, and the dogs were allowed to inhale wood smoke spontaneously from a specially designed apparatus. This apparatus enclosed only the dog's head. A wood fire was ignited in a remote combustion chamber, and
TABLE 1. Methods of Determination
Variable
Method of Measurement
Blood gases (Po,, Pco,, pH) V02 (oxygen consumption) Tidal volume Respiratory rate Expired CO2 Hemoglobin Vascular pressures
IL blood gas analyzer Collins' spirometer (5 minutes) Collins' spirometer Collins' spirometer Beckman medical gas analyzer Cyanmethemoglobin method Beckman dynograph and Statham strain gauges Harvard respirator (5 breaths)
Compliance5 Lung weight Lung per cent water
Weighing See text
Fourteen dogs were sacrificed at 4 hours for determination of weights, per cent of water and histologic examination of the lungs. Twelve dogs were sacrificed at 24 hours for similar data (one dog died on induction of anesthesia at 24 hours). Five dogs were scheduled to survive for 72 hours; however, two died between 48 and 72 hours. The latter seventeen dogs were extubated after 4 hours. Repeat anesthesia was necessary for the 24- and 72-hour measurements with recannulation of vessels and re-insertion of endotracheal tubes. In the event of death, anatomic data were recovered as soon as possible. Lung cultures were made from all the dying dogs. In 8 dogs, a crystalloid load of 10 mEq Na/kg (74.1 cc/kg) as Ringer's lactate was given in the 4 hours following smoke inhalation. Physiologic and anatomic variables were compared with the dogs sacrificed at 4 hours. Histologic examination was made of segments of several lobes from all dogs. The tissue was fixed in 10o formalin, inbedded in parafin and stained with hematoxylin and eosin.
smoke was conducted into the chamber containing the dog's head. With the temperature of the chamber being monitored (47.3 + 4.9 C), the dogs inhaled smoke for 5½-6 minutes. An 8-minute period of smoke inhalation was uniformly fatal. The dogs were removed from the chamber if bradypnea or apnea occurred. Most of the animals required immediate mechanical respiratory assistance to prevent death. Arterial blood gases obtained in the chamber were P02 36.7 + 11.0, PCo2 75.4 + 5.1 and Results pH 7.137 .026. Despite smoke inhalation to the point of near asphyxiaAt the end of the period of smoke inhalation, the dogs tion, no dog died before 4 hours, one dog of 12 died on were again intubated and immediately placed on 100%o induction of anesthesia at 24 hours and two of 5 died oxygen delivered by the Collins spirometer. After 30 between 48 and 72 hours. The two dying late had eviminutes the variables described in Tables 1 and 2 were dence of bacterial pneumonia. There was a significant determined. Percentage of water in the lung was obtained increase in lung weight at 4 hours as well as some inby taking small segments of the various lobes, weighing crease in lung water (Fig. 1). The changes in lung weight and drying to constant weight (3 days at 150 C). Then: ±
% H20
wet =
weight
-
dry weight
wet weight
TABLE 2. Calculated Variables
X 100
Oxygen consumption (V02) was determined after a 10-15 minute stabilization period of ventilation with 100o oxygen.
After the 30-minute measurements were taken, the animals were disconnected from the spirometer and allowed to breathe room air spontaneously until the next series of measurements. Determinations were obtained at 2, 4, 24 and 72 hours after injury.
Respiratory rate x tidal volume Expired Pco,-arterial Pco, arterial Pco, Fick Principle Cardiac output Blood 02 content ( [Hgb] x 1.34 x % 02 Sat.) + .0031 Po, Alveolar-arterial Po2gradientAlveolar Po,-arterial Po, (AA - a Poj) Alveolar P02 (Barometric pressure-47)-art. Pco2 Vascular resistance Arterial pressure-Vein pressure Cardiac output Minute volume Vd/Vt3
654
STEPHENSON AND OTHERS %
SURVIVAL
100
I7
80 60 A
l/2
C
4
2
722
24
LUNG WEIGHT gm/kg 18 r 16 -
14 12
-
-
_
InI
I
C 84
_
_
I
_
_
_
_
_
I
/2
2
_
Z
V
4
24
2
24
72
Ann. Surg. * November 1975
is shown by the increased respiratory rate and minute volume (Fig. 4). The animals continued to hyperventilate (increased minute volume) for at least 24 hours. The increased minute volume was primarily the result of increased tidal volume as rate tended to return to normal levels. Alterations in minute volume were not related to arterial P02 Pco2 or pH (Fig. 5). The ratio of dead space to tidal volume (Vd/Vt) was abnormal only at 30 minutes, returning rapidly to control values (Fig. 5). Cardiac output was decreased for the first 24 hours (Fig. 6). At 30 minutes the cardiac output was profoundly lowered, being less than one third of control. The lowered cardiac output was accompanied by slight but unsustained hypotension. Both systemic and pulmonary vascular resistance (Figs. 6 and 7) were substantially elevated for prolonged periods. Whereas MAP fell slight-
M 14-n
2
83 82 81
80 79
78
1'C '
1/2
'
2
'
{
4 HOURS
FIG. 1. (Top) No dog died within the first 4 hours after smoke inhalation. The only dog dying at 24 hours did so with the induction of anesthesia. The dogs dying at 72 hours died from pneumonia. (Center) Lung weights were elevated at 4, 24 and 72 hours after smoke inhalation. All elevations were statistically higher than normal. (Bottom) Lung per cent water was elevated at 4, 24 and 72 hours after smoke inhalation; however, gross pulmonary edema was unusual. *indicates statistically significant difference from control value (P
