452
Bums (1992) IS, (6), 452-455
find
in Great Britain
Roles of thromboxane and prostacyclin in the pathogenesis of acute respiratory failure in burn patients combined with inhalation injury Y.-S. Huang, A.(N.) Li and Z.-C. Yang Institute
of Bum Research, Southwestern
Hospital, Third Military Medical College of PLA, Chongqing,
Forty-one severely burned patients were divided into inhalation injuy and non-inhalation injury groups. If was found that in the inhalation injuy group, TXB, level and lXB,IG-hto-PGF,, ratio in both plasma and lung fissues were sign$cuntly elevated, circukzfoy platelet aggregate ratio greatlyincreased.Hisfopathologimarkedly decreased, and blood viscosity tally, congestion, oedema, haemorrhage and thrombosis were observed in lung fissues taken from patients succumbing to respiratory failure. The changes in TXB, and TXB,I6 kefo-PGF,, ratio accorded with the clinical course of fhe develomt of respiratory failure in bum patienfs wifh inhalation injury. If is proposed that the imbalance of 7XA,IPGI, plays an imporfant role in fhe pathogenesis of respiratoryfailure in severely burnt patients complicated with inhalation injury.
Introduction Inhalation injury is one of the important causes of death in bum patients. In the past decade, a number of experimental studies on mechanisms in the development of pulmonary oedema as well as acute respiratory failure after inhalation injury have been made (Shinozawa et al., 1986; Li et al., 1987; Yang, 1988; Wang et al., 1990). Recently, we investigated the roles of thromboxane (TX-A,) and prostacyclin (PGI,) in the pathogenesis of pulmonary oedema after smoke inhalation injury in goats (Huang et al., 1988a,b). However, as is well known clinically, many patients sustain inhalation injury and body surface bums simultaneously. In order to clarify the roles of TXA, and PGI, in the pathogenesis of pulmonary oedema and respiratory failure in such patients, we designed the prospective clinical study described in this report.
Materials and methods Forty-one severely burned patients admitted to our Institute between February 1987 and October 1988 were divided into two groups (Table I): an inhalation injury group (IBS group), which included those victims suffering from both inhalation injury (moderate or severe degree) and body surface burn complicated with respiratory failure within 7 days postbum; and a non-inhalation injury group (BS group), with body surface bums only. The IBS group had 10 patients (six males and four females). The average patient 0 1992 Butterworth-Heinemann 0305-4179/92/060452-04
Ltd
Sichuan, China
age was 36.5 f 11.7 (17-53) years and the average total burned surface area (TBSA) was 84.2 f 17.1 (45-98) per cent (Table 1). Of the 10 patients in the IBS group, three sustained moderate degrees of inhalation injury (including injury of the larynx, trachea and tracheal bifucation) and seven had severe degrees of inhalation injury (including injury extending down to the bronchi, terminal airways and even the alveolar spaces) in terms of the anatomical classification (Bum Research Unit, Third Military Medical College, 1977). Both nasotracheal intubation and tracheostomy were performed on five patients respectively. Seven patients required mechanical ventilation (using a synchronous jet respirator; Fifth Machine Tool Factory, Jiangxi, China) and three needed oxygen inspiration to meet their oxygen requirements after intubation or tracheostomy. Nine of the 10 patients in the IBS group died of respiratory failure, whereas all of the patients in the BS group survived. Conventional treatment established in our Institute was given to all patients in both groups after admission. Samples for variable studies were collected at the intervals shown in Table II.
Levels of TXB,, the stable degradation product of TXA,, and 6-keto-PGF,,, the stable degradation product of PGI,, in plasma and lung tissues were measured by radioimmunoassay techniques (Li et al., 1985). Syringes and test-tubes used to collect blood samples for the determination of TXB, and 6-keto-PGF,, were siliconized in advance. Before collecting blood samples, the siliconized syringe was solution. moistened with 0.2 ml of indomethacin-heparin
Table I. General data Group ’
Patients (no.1
Age WI t
Burn surface area CW t
IBS
10 (6M, 4F)
BS
31 (21 M, 1OF)
36.5k11.7 (17-53) 29.3*11.0 (16-58)
84.2zk17.1 (45-98) 62.3 f 22.1 (30-98)
llBS, body surface burns combined with inhalation injury (moderate and severe degree) developing respiratory failure within 7 PBD; BS, body surface burns only. WesuIts given are mean f s.e.m. with range in parentheses.
Huang et al.: Inhalation injury and acute respiratory failure
453
Table II. Variables determined and their times after injury Days postburn 0.5
Plasma TXB,, 6-keto- PG F,, CPAR Blood viscosity Blood gases Lung tissue TXB,, 6-keto-PGF,, Pathomorphology of lung tissues
1
2
3
5
7
++++++ ++++++ ++++++ ++++++ immediately after death immediately after death
Then blood was drawn with the syringe from a peripheral vein and mixed, and then poured into a siliconized test-tube, and centrifuged for 15 min (4”C, 1500g). The plasma was extracted twice with ethyl acetate. The extracts, after drying in a vacuum desicator, were available for TXB, and 6-keto-PGF,, determination (Li et al., 1985). Circulatory platelet aggregate ratio (CPAR) was determined by the method of Wu and Hoak (1974). Blood viscosity was assayed by a viscosity machine (Model NZ-4, Analysis Instrument Factory, Tianjin, PR China). For determination of blood viscosity, the viscosity machine was preheated for z min. Then 0.6 ml of whole blood was added into the test cup of the machine. The cone-shaped sensor was then lowered until it just made contact with the blood in the test cup. At this time the cone rotated at SO r.p.m. The attached electrical recording meter, previously set at zero, was then adjusted back to zero, the required adjustment being proportional to the shear rate (i.e. viscosity) of the blood. Arterial blood gases were determined in a blood gas analyser (Model 1303, Instrumentation Laboratory, USA). Pathomorphological changes of the tracheobronchial tree and lung tissues of six patients in the IBS group who died due to respiratory failure were examined both grossly and by light microscopy. All variables are presented as mean value f s.e.m. Data were compared using the f test and analysis of variance (ANOVA). Probabilities less than 0.05 and 0.01 were considered significant and very significant respectively.
OL
Oo.51
i Days
Figure 1. Dynamic changes of plasma TXB,, 6-keto-PGF,, and BS(-.-) patients. (6-k-p) and TXB,/6-k-p ratio in IBS( -) ‘P-c 0.05, “P-c 0.01.
2.5
200
z
150
2 3 F 2
100
5 F if
r
50
Results Clinical manifestations In patients of the IBS group, the pattern and/or rate of respiration altered. There was dyspnoea, irregularity of respiration and in severe injuries even apnoea developing early. Broncheotracheal secretions increased profoundly. Moist rales could be heard all over the chest. All of the 10 patients developed respiratory failure, eight within days 3-7 postbum and two on the first day postbum. Patients with severe degrees of inhalation injury developed respiratory failure earlier than those with only moderate injuries, Plasma TXB,, 6-keto-PGF,, and TXBJG-keto-PGF,, ratio At I2 h postburn, the plasma levels of TXB, in the IBS group increased abruptly to 3107 f 385 pg/ml, which was sign& cantly higher than that in the BS group, then gradually declined before rising again on day 3 postbum and persisting at high levels until the end of the study, on day 7 postbum. There were no significant differences in 6-ketoPGF,, levels between the two groups. Values of TXB,/6keto-PGF,, ratio in patients of the IBS group at different time intervals were also markedly higher than those in
postburn
0
0 TX62
1
6-k-P
TXB2/6-k-P ratio
Figure 2. Levels of lung tissue TXB,, 6-keto-PGF,, (6-k-p) and TXB,/&k-p ratio. *‘PC 0.01. q Jl,IBS cases; 0, control.
patients of the BS group, and showed two peaks, one on the first and the other between days 3 and 7 postbum (Figure I). Lung tissue TXB,, 6-keto-PGF,, and TXBJG-ketoPGF,, ratio As is shown in Figwe2, the levels of both TXB, and the TXBJbketo-PGF,, ratio in lung tissues taken from IBS patients who died from respiratory failure were higher than those in control subjects (six patients dying early from severe brain injury served as controls). Circulatory platelet aggregate ratio (CPAR) The levels of CPAR in the IBS group, as shown in Figure 3, decreased markedly and were much lower than those in the BS patients.
Burns (1992) Vol. l&~/No.6
454
01
0.5
I
I
I
1
2
3
Days
,I
"
I
I
5
7
postburn
Figure 3. Changes of circulatory platelet aggregate ratio (CPAR) in IBS (-) and BS(-.-) patients. *P
Bums (1992) IS, (6), 452-455
find
in Great Britain
Roles of thromboxane and prostacyclin in the pathogenesis of acute respiratory failure in burn patients combined with inhalation injury Y.-S. Huang, A.(N.) Li and Z.-C. Yang Institute
of Bum Research, Southwestern
Hospital, Third Military Medical College of PLA, Chongqing,
Forty-one severely burned patients were divided into inhalation injuy and non-inhalation injury groups. If was found that in the inhalation injuy group, TXB, level and lXB,IG-hto-PGF,, ratio in both plasma and lung fissues were sign$cuntly elevated, circukzfoy platelet aggregate ratio greatlyincreased.Hisfopathologimarkedly decreased, and blood viscosity tally, congestion, oedema, haemorrhage and thrombosis were observed in lung fissues taken from patients succumbing to respiratory failure. The changes in TXB, and TXB,I6 kefo-PGF,, ratio accorded with the clinical course of fhe develomt of respiratory failure in bum patienfs wifh inhalation injury. If is proposed that the imbalance of 7XA,IPGI, plays an imporfant role in fhe pathogenesis of respiratoryfailure in severely burnt patients complicated with inhalation injury.
Introduction Inhalation injury is one of the important causes of death in bum patients. In the past decade, a number of experimental studies on mechanisms in the development of pulmonary oedema as well as acute respiratory failure after inhalation injury have been made (Shinozawa et al., 1986; Li et al., 1987; Yang, 1988; Wang et al., 1990). Recently, we investigated the roles of thromboxane (TX-A,) and prostacyclin (PGI,) in the pathogenesis of pulmonary oedema after smoke inhalation injury in goats (Huang et al., 1988a,b). However, as is well known clinically, many patients sustain inhalation injury and body surface bums simultaneously. In order to clarify the roles of TXA, and PGI, in the pathogenesis of pulmonary oedema and respiratory failure in such patients, we designed the prospective clinical study described in this report.
Materials and methods Forty-one severely burned patients admitted to our Institute between February 1987 and October 1988 were divided into two groups (Table I): an inhalation injury group (IBS group), which included those victims suffering from both inhalation injury (moderate or severe degree) and body surface burn complicated with respiratory failure within 7 days postbum; and a non-inhalation injury group (BS group), with body surface bums only. The IBS group had 10 patients (six males and four females). The average patient 0 1992 Butterworth-Heinemann 0305-4179/92/060452-04
Ltd
Sichuan, China
age was 36.5 f 11.7 (17-53) years and the average total burned surface area (TBSA) was 84.2 f 17.1 (45-98) per cent (Table 1). Of the 10 patients in the IBS group, three sustained moderate degrees of inhalation injury (including injury of the larynx, trachea and tracheal bifucation) and seven had severe degrees of inhalation injury (including injury extending down to the bronchi, terminal airways and even the alveolar spaces) in terms of the anatomical classification (Bum Research Unit, Third Military Medical College, 1977). Both nasotracheal intubation and tracheostomy were performed on five patients respectively. Seven patients required mechanical ventilation (using a synchronous jet respirator; Fifth Machine Tool Factory, Jiangxi, China) and three needed oxygen inspiration to meet their oxygen requirements after intubation or tracheostomy. Nine of the 10 patients in the IBS group died of respiratory failure, whereas all of the patients in the BS group survived. Conventional treatment established in our Institute was given to all patients in both groups after admission. Samples for variable studies were collected at the intervals shown in Table II.
Levels of TXB,, the stable degradation product of TXA,, and 6-keto-PGF,,, the stable degradation product of PGI,, in plasma and lung tissues were measured by radioimmunoassay techniques (Li et al., 1985). Syringes and test-tubes used to collect blood samples for the determination of TXB, and 6-keto-PGF,, were siliconized in advance. Before collecting blood samples, the siliconized syringe was solution. moistened with 0.2 ml of indomethacin-heparin
Table I. General data Group ’
Patients (no.1
Age WI t
Burn surface area CW t
IBS
10 (6M, 4F)
BS
31 (21 M, 1OF)
36.5k11.7 (17-53) 29.3*11.0 (16-58)
84.2zk17.1 (45-98) 62.3 f 22.1 (30-98)
llBS, body surface burns combined with inhalation injury (moderate and severe degree) developing respiratory failure within 7 PBD; BS, body surface burns only. WesuIts given are mean f s.e.m. with range in parentheses.
Huang et al.: Inhalation injury and acute respiratory failure
453
Table II. Variables determined and their times after injury Days postburn 0.5
Plasma TXB,, 6-keto- PG F,, CPAR Blood viscosity Blood gases Lung tissue TXB,, 6-keto-PGF,, Pathomorphology of lung tissues
1
2
3
5
7
++++++ ++++++ ++++++ ++++++ immediately after death immediately after death
Then blood was drawn with the syringe from a peripheral vein and mixed, and then poured into a siliconized test-tube, and centrifuged for 15 min (4”C, 1500g). The plasma was extracted twice with ethyl acetate. The extracts, after drying in a vacuum desicator, were available for TXB, and 6-keto-PGF,, determination (Li et al., 1985). Circulatory platelet aggregate ratio (CPAR) was determined by the method of Wu and Hoak (1974). Blood viscosity was assayed by a viscosity machine (Model NZ-4, Analysis Instrument Factory, Tianjin, PR China). For determination of blood viscosity, the viscosity machine was preheated for z min. Then 0.6 ml of whole blood was added into the test cup of the machine. The cone-shaped sensor was then lowered until it just made contact with the blood in the test cup. At this time the cone rotated at SO r.p.m. The attached electrical recording meter, previously set at zero, was then adjusted back to zero, the required adjustment being proportional to the shear rate (i.e. viscosity) of the blood. Arterial blood gases were determined in a blood gas analyser (Model 1303, Instrumentation Laboratory, USA). Pathomorphological changes of the tracheobronchial tree and lung tissues of six patients in the IBS group who died due to respiratory failure were examined both grossly and by light microscopy. All variables are presented as mean value f s.e.m. Data were compared using the f test and analysis of variance (ANOVA). Probabilities less than 0.05 and 0.01 were considered significant and very significant respectively.
OL
Oo.51
i Days
Figure 1. Dynamic changes of plasma TXB,, 6-keto-PGF,, and BS(-.-) patients. (6-k-p) and TXB,/6-k-p ratio in IBS( -) ‘P-c 0.05, “P-c 0.01.
2.5
200
z
150
2 3 F 2
100
5 F if
r
50
Results Clinical manifestations In patients of the IBS group, the pattern and/or rate of respiration altered. There was dyspnoea, irregularity of respiration and in severe injuries even apnoea developing early. Broncheotracheal secretions increased profoundly. Moist rales could be heard all over the chest. All of the 10 patients developed respiratory failure, eight within days 3-7 postbum and two on the first day postbum. Patients with severe degrees of inhalation injury developed respiratory failure earlier than those with only moderate injuries, Plasma TXB,, 6-keto-PGF,, and TXBJG-keto-PGF,, ratio At I2 h postburn, the plasma levels of TXB, in the IBS group increased abruptly to 3107 f 385 pg/ml, which was sign& cantly higher than that in the BS group, then gradually declined before rising again on day 3 postbum and persisting at high levels until the end of the study, on day 7 postbum. There were no significant differences in 6-ketoPGF,, levels between the two groups. Values of TXB,/6keto-PGF,, ratio in patients of the IBS group at different time intervals were also markedly higher than those in
postburn
0
0 TX62
1
6-k-P
TXB2/6-k-P ratio
Figure 2. Levels of lung tissue TXB,, 6-keto-PGF,, (6-k-p) and TXB,/&k-p ratio. *‘PC 0.01. q Jl,IBS cases; 0, control.
patients of the BS group, and showed two peaks, one on the first and the other between days 3 and 7 postbum (Figure I). Lung tissue TXB,, 6-keto-PGF,, and TXBJG-ketoPGF,, ratio As is shown in Figwe2, the levels of both TXB, and the TXBJbketo-PGF,, ratio in lung tissues taken from IBS patients who died from respiratory failure were higher than those in control subjects (six patients dying early from severe brain injury served as controls). Circulatory platelet aggregate ratio (CPAR) The levels of CPAR in the IBS group, as shown in Figure 3, decreased markedly and were much lower than those in the BS patients.
Burns (1992) Vol. l&~/No.6
454
01
0.5
I
I
I
1
2
3
Days
,I
"
I
I
5
7
postburn
Figure 3. Changes of circulatory platelet aggregate ratio (CPAR) in IBS (-) and BS(-.-) patients. *P
