Sepsis, Resuscitated Hemorrhagic Shock and "Shock Lung:"1 An Experimental Correlation BARRY C. ESRIG, M.D., ROBERT L. FULTON, M.D.*
Dogs were submitted to hemorrhagic shock, resuscitated shock and resuscitated shock plus a pulmonary bacterial insult. Pulmonary failure was absent in dogs submitted only to shock or to shock and its resuscitation. The addition of usually sub-lethal amounts of micro-organisms to the shock-resuscitated lung caused rapid death from pulmonary failure. Pulmonary failure was demonstrated by increased lung weight, hypoxemia, decreased compliance and a hemorrhagic destruction of lung tissue. These findings strongly support recent concepts of an infective genesis of "shock lung" in man.
DULMONARY FAILURE following shock, trauma and difI ficult surgical procedures is a frequent cause of morbidity and mortality.11'24 It has become evident that such lung failure is usually associated with bacterial infection, either pulmonary or remote.1"8'32 The ability to produce pulmonary changes with hemorrhagic shock,2123 large volume fluid infusion5"19 and intravenous injection of vaso-destructive products3"7'27 in the laboratory is well established. However, most of these investigations do not closely mimic clinical shock, its treatment or the
occasionally occurring pulmonary failure. A causative association between hemorrhagic shock and pulmonary failure, so-called "shock lung," has been questioned by several investigators.6'1"'2'18 Even most enthusiastic advocates of "shock lung" have not been able to produce lethal lung failure purely from hemorrhagic shock. Although some physiologic and anatomic
From the Price Institute of Surgical Research and the Department of Surgery University of Louisville School of Medicine Health Sciences Center, Louisville, Kentucky
changes are evident in the lung during hemorrhagic shock,23'3' dogs dying of hypovolemia can be fully oxygenated until death.10"12"13 Essentially all patients in whom post-traumatic pulmonary insufficiency occurs develop extrapulmonary or respiratory tract sepsis4""26 before or concurrently with lung failure. Even though Clowes and others5 have shown experimentally that peritonitis with septic shock will lead to lung failure, no experimental association of hemorrhagic shock, bacterial infection and the occurrence of pulmonary insufficiency exists. The purpose of the present experiment was to determine if the shocked-resuscitated animal is more susceptible to pulmonary sepsis and failure than the normal animal. It was found that shock and crystalloid-resuscitated shock do not produce true lung failure and that the shock-resuscitated lung was more susceptible to pulmonary sepsis and subsequent failure than the normal organ.
Methods Conditioned mongrel dogs weighing 13-30 kg were diPresented at the Annual Meeting of the American Surgical Associa- vided into four groups. Group I (shock only) was submittion, Quebec City, Quebec, May 7-9, 1975. ted to a modified Wiggers' type of hemorrhagic shock, Reprint requests: Robert L. Fulton, M.D. The Department of only shed blood following the period of receiving Surgery, University of Louisville School of Medicine, Health Sciences These animals were monitored until death hypotension. Center, Louisville, Kentucky 40201. occurred or was clearly imminent. Group II (resuscitated *Sponsored by Hiram C. Polk, Jr., M.D.
218
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TABLE 1. Physiologic Variables Determined.
Method of Measurement Variable MAP (arterial pressure) Statham 23 Db strain gauge PAP (pulmonary arterial pressure) connected to Beckman PWP (pulmonary wedge pressure) Dynograph R411 Arterial and venous blood gases Instruments Laboratory (IL) blood gas analyzer Po2, Pco2, pH (Model 113) Beckman medical gas analyzer Alveolar % COQ (10 breaths) Hemoglobin Tidal volume Respiratory rate Oxygenation consumption Compliance
Cyanmethemoglobin method Collins' spirometer Delivering 100lo 02 after 10 minutes' stabilization Harvard respirator With airway clamped. Pressure measured with strain gauge and Dynograph"
219 (bacteria only) received the intra-tracheal injection of Pseudomonas aeruginosa after cardiovascular and pulmonary function had been determined. The variables were remeasured 24 and 48 hours later. At 48 hours, the dogs were sacrificed. After death or following sacrifice, both lungs were excised and weighed. Small segments were removed for histologic examination (formalin fixation; hemotoxylin and eosin stain). Other segments were taken, weighed and dried at 150 C for 3 days for determination of per cent water: % H20=Wet Weight - Dry Weight Wet Weight From the data obtained from the measured variables, the functions shown in Table 2 were obtained. Cardiac output was calculated from oxygen consumption measured with the spirometer using 100% 02 over a fiveminute period. The arterial and venous 02 content was determined from the hemoglobin, Po2 and pH measurements. Saturation was obtained using a standard nomogram. Blood 02 content (Cx) = (1.34 x Hgb x % 02 saturation) + .0031 P02. Alveolar Pco2 is obtained from the percent of CO2 in mixed expired air (average 10 breaths): (Barometric pressure 47 mm Hg) x % CO2 = Alveolar PC02 The ventilation-perfusion ratio (Va/Qc) was estimated from the end capillary and venous 02 content, the inspired fraction of 02 (F102) and the alveolar fraction of 02: FAO2 = (Barometric Pressure-47 mm HG-Paco,)/ Barometric Pressure. This determination, made with an F102 of 1.0, was uncorrected for differences in inspired and expired air and represents only an estimate7 of ventilated-to-perfused lung tissue. The physiologic variables obtained from living animals must be considered to represent the maximum numerical mean in any particular group. The variables were compared to control values and between groups using the two-tailed Student's t test. Significance of mortality differences between groups was compared using the Yates'
shock) differed from Group I in that the shed blood was supplemented by a large amount of intravenous Ringer's lactate (R/L) solution (17 mEq Na/kg). Group III (shock and bacteria) was submitted to shock, resuscitated with R/L and blood and then given an intra-tracheal injection of 2 x 109 Pseudomonas aeruginosa organisms. The fourth group of dogs (bacteria only) received an intratracheal injection of pseudomonas. The later three groups were monitored for 48 hours. The dogs were given intravenous pentobarbital (30 mg/kg) and the tracheae were intubated. Arterial pressure (MAP) was measured with femoral artery cannulas. A Swan-Ganz catheter was introduced into the pulmonary artery from the jugular vein. A femoral vein cannula was placed for withdrawal and infusion of blood and solutions. After preparation, the variables listed in Table 1 were measured. Following initial (control) measurements, the dogs in Groups I, II and III were rapidly bled to a MAP of 50-60 mm Hg. This pressure was maintained for 90 minutes after which time the MAP was lowered to 30 mm Hg for an additional 60 minutes. At the end of this time all variables were measured. In Group I (shock only -8 dogs), all of the shed blood was returned in a 30minute period. In Groups 11 (7 dogs) and III (8 dogs), the corrected Chi-squared analysis.8 shed blood plus 74 ml/kg R/L was given in the 30-minute period. At the end of this period (pTX), the physiologic TABLE 2. Calculated Variables. measurements were repeated. Group I received no Fick Principle Cardiac Output further treatment, and measurements were obtained at 2, 4 and 6 hours following re-infusion of blood. Groups II Alveolar Pco2 Part CO2 and III received additional R/L (52 ml/kg) in a four-hour Vd/Vt (dead space ratio) Alveolar Pco2 period with determinations made at 2 and 4 hours. At the Minute Volume Tidal Volume x Respiratory Rate end of 4 hours, the Group II animals were returned to Va/Qc (VentilationCECO2 - CVO2 their cages. The Group III dogs received pseudomonas F10, - FAO2 Perfusion ratio)7 intra-tracheally before being returned to their cages. The PAP - PWP (Pulmonary surviving dogs were re-examined at 24 and 48 hours, and PVR Vascular Resistance) Cardiac Output survivors were sacrificed at 48 hours. The Group IV dogs -
ESRIG AND FULTON
220
Ann. Surg. * September 1975
%S MORTALITY Blood Only Resuscitated Shock Shock + Bacteria x--..-x Bacteria Only
FIG. 1. The mortality rate of the four groups of dogs is shown. At 48 hours, all of the "shock-plusbacteria" dogs had died either of sepsis or pulmonary failure. * indicates that the mortality was significantly (P
Dogs were submitted to hemorrhagic shock, resuscitated shock and resuscitated shock plus a pulmonary bacterial insult. Pulmonary failure was absent in dogs submitted only to shock or to shock and its resuscitation. The addition of usually sub-lethal amounts of micro-organisms to the shock-resuscitated lung caused rapid death from pulmonary failure. Pulmonary failure was demonstrated by increased lung weight, hypoxemia, decreased compliance and a hemorrhagic destruction of lung tissue. These findings strongly support recent concepts of an infective genesis of "shock lung" in man.
DULMONARY FAILURE following shock, trauma and difI ficult surgical procedures is a frequent cause of morbidity and mortality.11'24 It has become evident that such lung failure is usually associated with bacterial infection, either pulmonary or remote.1"8'32 The ability to produce pulmonary changes with hemorrhagic shock,2123 large volume fluid infusion5"19 and intravenous injection of vaso-destructive products3"7'27 in the laboratory is well established. However, most of these investigations do not closely mimic clinical shock, its treatment or the
occasionally occurring pulmonary failure. A causative association between hemorrhagic shock and pulmonary failure, so-called "shock lung," has been questioned by several investigators.6'1"'2'18 Even most enthusiastic advocates of "shock lung" have not been able to produce lethal lung failure purely from hemorrhagic shock. Although some physiologic and anatomic
From the Price Institute of Surgical Research and the Department of Surgery University of Louisville School of Medicine Health Sciences Center, Louisville, Kentucky
changes are evident in the lung during hemorrhagic shock,23'3' dogs dying of hypovolemia can be fully oxygenated until death.10"12"13 Essentially all patients in whom post-traumatic pulmonary insufficiency occurs develop extrapulmonary or respiratory tract sepsis4""26 before or concurrently with lung failure. Even though Clowes and others5 have shown experimentally that peritonitis with septic shock will lead to lung failure, no experimental association of hemorrhagic shock, bacterial infection and the occurrence of pulmonary insufficiency exists. The purpose of the present experiment was to determine if the shocked-resuscitated animal is more susceptible to pulmonary sepsis and failure than the normal animal. It was found that shock and crystalloid-resuscitated shock do not produce true lung failure and that the shock-resuscitated lung was more susceptible to pulmonary sepsis and subsequent failure than the normal organ.
Methods Conditioned mongrel dogs weighing 13-30 kg were diPresented at the Annual Meeting of the American Surgical Associa- vided into four groups. Group I (shock only) was submittion, Quebec City, Quebec, May 7-9, 1975. ted to a modified Wiggers' type of hemorrhagic shock, Reprint requests: Robert L. Fulton, M.D. The Department of only shed blood following the period of receiving Surgery, University of Louisville School of Medicine, Health Sciences These animals were monitored until death hypotension. Center, Louisville, Kentucky 40201. occurred or was clearly imminent. Group II (resuscitated *Sponsored by Hiram C. Polk, Jr., M.D.
218
VOl. 182 NO. 3
SEPSIS AND "SHOCK LUNG"
-
TABLE 1. Physiologic Variables Determined.
Method of Measurement Variable MAP (arterial pressure) Statham 23 Db strain gauge PAP (pulmonary arterial pressure) connected to Beckman PWP (pulmonary wedge pressure) Dynograph R411 Arterial and venous blood gases Instruments Laboratory (IL) blood gas analyzer Po2, Pco2, pH (Model 113) Beckman medical gas analyzer Alveolar % COQ (10 breaths) Hemoglobin Tidal volume Respiratory rate Oxygenation consumption Compliance
Cyanmethemoglobin method Collins' spirometer Delivering 100lo 02 after 10 minutes' stabilization Harvard respirator With airway clamped. Pressure measured with strain gauge and Dynograph"
219 (bacteria only) received the intra-tracheal injection of Pseudomonas aeruginosa after cardiovascular and pulmonary function had been determined. The variables were remeasured 24 and 48 hours later. At 48 hours, the dogs were sacrificed. After death or following sacrifice, both lungs were excised and weighed. Small segments were removed for histologic examination (formalin fixation; hemotoxylin and eosin stain). Other segments were taken, weighed and dried at 150 C for 3 days for determination of per cent water: % H20=Wet Weight - Dry Weight Wet Weight From the data obtained from the measured variables, the functions shown in Table 2 were obtained. Cardiac output was calculated from oxygen consumption measured with the spirometer using 100% 02 over a fiveminute period. The arterial and venous 02 content was determined from the hemoglobin, Po2 and pH measurements. Saturation was obtained using a standard nomogram. Blood 02 content (Cx) = (1.34 x Hgb x % 02 saturation) + .0031 P02. Alveolar Pco2 is obtained from the percent of CO2 in mixed expired air (average 10 breaths): (Barometric pressure 47 mm Hg) x % CO2 = Alveolar PC02 The ventilation-perfusion ratio (Va/Qc) was estimated from the end capillary and venous 02 content, the inspired fraction of 02 (F102) and the alveolar fraction of 02: FAO2 = (Barometric Pressure-47 mm HG-Paco,)/ Barometric Pressure. This determination, made with an F102 of 1.0, was uncorrected for differences in inspired and expired air and represents only an estimate7 of ventilated-to-perfused lung tissue. The physiologic variables obtained from living animals must be considered to represent the maximum numerical mean in any particular group. The variables were compared to control values and between groups using the two-tailed Student's t test. Significance of mortality differences between groups was compared using the Yates'
shock) differed from Group I in that the shed blood was supplemented by a large amount of intravenous Ringer's lactate (R/L) solution (17 mEq Na/kg). Group III (shock and bacteria) was submitted to shock, resuscitated with R/L and blood and then given an intra-tracheal injection of 2 x 109 Pseudomonas aeruginosa organisms. The fourth group of dogs (bacteria only) received an intratracheal injection of pseudomonas. The later three groups were monitored for 48 hours. The dogs were given intravenous pentobarbital (30 mg/kg) and the tracheae were intubated. Arterial pressure (MAP) was measured with femoral artery cannulas. A Swan-Ganz catheter was introduced into the pulmonary artery from the jugular vein. A femoral vein cannula was placed for withdrawal and infusion of blood and solutions. After preparation, the variables listed in Table 1 were measured. Following initial (control) measurements, the dogs in Groups I, II and III were rapidly bled to a MAP of 50-60 mm Hg. This pressure was maintained for 90 minutes after which time the MAP was lowered to 30 mm Hg for an additional 60 minutes. At the end of this time all variables were measured. In Group I (shock only -8 dogs), all of the shed blood was returned in a 30minute period. In Groups 11 (7 dogs) and III (8 dogs), the corrected Chi-squared analysis.8 shed blood plus 74 ml/kg R/L was given in the 30-minute period. At the end of this period (pTX), the physiologic TABLE 2. Calculated Variables. measurements were repeated. Group I received no Fick Principle Cardiac Output further treatment, and measurements were obtained at 2, 4 and 6 hours following re-infusion of blood. Groups II Alveolar Pco2 Part CO2 and III received additional R/L (52 ml/kg) in a four-hour Vd/Vt (dead space ratio) Alveolar Pco2 period with determinations made at 2 and 4 hours. At the Minute Volume Tidal Volume x Respiratory Rate end of 4 hours, the Group II animals were returned to Va/Qc (VentilationCECO2 - CVO2 their cages. The Group III dogs received pseudomonas F10, - FAO2 Perfusion ratio)7 intra-tracheally before being returned to their cages. The PAP - PWP (Pulmonary surviving dogs were re-examined at 24 and 48 hours, and PVR Vascular Resistance) Cardiac Output survivors were sacrificed at 48 hours. The Group IV dogs -
ESRIG AND FULTON
220
Ann. Surg. * September 1975
%S MORTALITY Blood Only Resuscitated Shock Shock + Bacteria x--..-x Bacteria Only
FIG. 1. The mortality rate of the four groups of dogs is shown. At 48 hours, all of the "shock-plusbacteria" dogs had died either of sepsis or pulmonary failure. * indicates that the mortality was significantly (P
